AIM To investigate the effect of Boschniakiarossica（BR）extract on expression of GST-P,p53 and p21<sup>ras</sup>proteins in early stage of chemicalhepatocarcinogenesis in rats and its anti-inflammatory ac...AIM To investigate the effect of Boschniakiarossica（BR）extract on expression of GST-P,p53 and p21<sup>ras</sup>proteins in early stage of chemicalhepatocarcinogenesis in rats and its anti-inflammatory activities.METHODS The expression of tumor marker-placental form glutathione S-transferase（GST-P）,p53 and p21<sup>ras</sup>proteins were investigated byimmunohistochemical techniques and ABCmethod.Anti-inflammatory activities of BR werestudied by xylene and croton oil-induced mouseear edema,carrageenin,histamine and hotscald-induced rat pow edema,adjuvant-inducedrat arthritis and cotton pellet-induced mousegranuloma formation methods.RESULTS The 500 mg/kg of BR-H<sub>2</sub>O extractfractionated from BR-Methanol extract hadinhibitory effect on the formation of DEN-inducedGST-P-positive foci in rat liver（GST-P stainingwas 78% positive in DEN+AAF group vs 20%positive in DEN+AAF+BR group,P【0.05）andthe expression of mutant p53 and p21<sup>ras</sup>proteinwas lower than that of hepatic preneoplasticlesions（33% and 22% positive respectively inDEN+AAF group vs negative in DEN+AAF+BRgroup）.Both CH<sub>2</sub>Cl<sub>2</sub> and H<sub>2</sub>O extracts from BRhad anti-inflamatory effect in xylene and crotonoil-induced mouse ear edema（inhibitory rateswere 26%-29% and 35%-59%,respectively）. BR-H<sub>2</sub>O extract exhibited inhibitory effect incarrageenin,histamine and hot scald-inducedhind paw edema and adjuvant-induced arthritis inrats and cotton pellet-induced granulomaformation in mice.CONCLUSION BR extract exhibited inhibitory effect on formation of preneoplastic hepatic foci in early stage of rat chemical hepato-carcinogenesis. Both CH<sub>2</sub>CI<sub>2</sub> and H<sub>2</sub>O extracts from BR exerted anti-inflammatory effect in rats and mice.展开更多
BACKGROUND: Enzymes involved in drug and xenobiotic metabolism have been considered to exist in two groups: phase I and phase II enzymes. Cytochrome P450 isoenzymes (CYPs) are the most important phase I enzymes in the...BACKGROUND: Enzymes involved in drug and xenobiotic metabolism have been considered to exist in two groups: phase I and phase II enzymes. Cytochrome P450 isoenzymes (CYPs) are the most important phase I enzymes in the metabolism of xenobiotics. The products of phase I metabolism are then acted upon by phase II enzymes, including glutathione S-transferases (GSTs). Herbs that inhibit CYPs such as CYP3A4 or that induce GSTs may have the potential to protect against chemical carcinogenesis since the mutagenic effects of carcinogens are often mediated through an excess of CYP-generated reactive intermediates. This study was designed to investigate the effects of salvianolic acid B (Sal B), a pure compound extracted from Radix Salviae Miltiorrhizae, a Chinese herb, on cell proliferation and CYP1A2 and CYP3A4 mRNA expression in the presence or absence of rifampicin, a potent inducer of CYPs and GST protein expression in HepG2 cells. METHODS: HepG2 cells were incubated with different concentrations of Sal B. Cell proliferation was determined by SYTOX-Green nucleic acid staining. CYP3A4 and CYP1A2 mRNA expression was assayed by real-time PCR. GST protein expression was analyzed by Western blotting. RESULTS: Low concentrations of Sal B (0-20 μmol/L) had no significant effects on cell proliferation, while higher concentrations (100-250 μmol/L) significantly inhibited proliferation in a concentration-dependent manner. Ten μmol/L Sal B, but not 1 μmol/L, down-regulated CYP3A4 and CYP1A2 mRNA expression after 24 hours of incubation, whereas both 1 and 10 μmol/L Sal B down-regulated CYP3A4mRNA expression after 96 hours of incubation; moreover, 1 and 10 μmol/L Sal B inhibited CYP3A4 mRNA expression induced by rifampicin. Both 1 μmol/L and 10 μmol/L Sal B increased GST expression. CONCLUSION: Sal B inhibits CYP3A4 and CYP1A2 mRNA expression and induces GST expression in HepG2 cells.展开更多
AIM：To explore the expressions of GST-π and telomerase activity in esophageal carcinoma and premalignant lesions and to investigate the value of endoscopic methylene blue （MB） and Lugol＇s iodine double staining. ...AIM：To explore the expressions of GST-π and telomerase activity in esophageal carcinoma and premalignant lesions and to investigate the value of endoscopic methylene blue （MB） and Lugol＇s iodine double staining. METHODS： Seventy-two patients with esophagopathy were sprayed endoscopically with MB and Lugol＇s iodine in proper order and the areas stained blue and brown, and the area between the blue and brown stains were obtained. Depending on the pattern of mucosal staining, biopsy specimen was obtained. GST-π and telomerase activity in specimens were examined by immunohistochemistry and PCR-based silver staining telomeric repeat amplification protocol, respectively. RESULTS： After MB and Lugol＇s iodine staining, the area between both the colors was obtained in 64 of the 72 patients and the areas were stained blue and brown in all of the 72 patients. Association test of two simultaneous ordinal categorical data showed a correlation between the esophageal mucosal staining and the esophageal histology （P〈0.005）. The expression of GST-π and telomerase activity in esophageal carcinoma and premalignant lesions increased. The expression of GST-π and telomerase activity in dysplasia and carcinoma was significantly higher than that in normal epithelium （P〈0.005）. The expression in hyperplasia was slightly higher than that in normal epithelium. With the lesions progressing from low- to moderate- to high-grade dysplasia, the positive rate increased （P〈0.025）. Expression of GST-π was correlated with that of telomerase activity in dysplasia and carcinoma （φ= 0.4831, P〈0.005;φ= 0.3031, P〈0.025, respectively）; but there was no correlation between them in normal epithelium and hyperplasia. CONCLUSION： The expression of GST-π and telomerase may be an early event in the carcinogenesis of esophagus. They may play an induced and synergistic role with each other in the carcinogenesis of esophagus. Endoscopic MB and Lugol＇s iodine double staining and detection of GST-π and telomera展开更多
Breast cancer is the most common malignancy in women worldwide.Triplenegative breast cancer(TNBC),refers breast cancer negative for estrogen receptor,progesterone receptor and human epidermal growth factor receptor 2,...Breast cancer is the most common malignancy in women worldwide.Triplenegative breast cancer(TNBC),refers breast cancer negative for estrogen receptor,progesterone receptor and human epidermal growth factor receptor 2,characterized by high drug resistance,high metastasis and high recurrence,treatment of which is a difficult problem in the clinical treatment of breast cancer.In order to better treat TNBC clinically,it is a very urgent task to explore the mechanism of TNBC resistance in basic breast cancer research.Pregnane X receptor(PXR)is a nuclear receptor whose main biological function is to participate in the metabolism,transport and clearance of allobiological agents in PXR.PXR plays an important role in drug metabolism and clearance,and PXR is highly expressed in tumor tissues of TNBC patients,which is related to the prognosis of breast cancer patients.This reviews synthesized the important role of PXR in the process of high drug resistance to TNBC chemotherapeutic drugs and related research progress.展开更多
The brown planthopper （BPH）, Nilaparvata lugens （Stal）, is one of the major pests of rice throughout Asia. Extensive use of insecticides for suppressing N. lugens has resulted in the development of insecticide res...The brown planthopper （BPH）, Nilaparvata lugens （Stal）, is one of the major pests of rice throughout Asia. Extensive use of insecticides for suppressing N. lugens has resulted in the development of insecticide resistance leading to frequent control failures in the field. The aim of the present study was to evaluate resistance in the field populations of N. lugens from major rice growing states of South India to various insecticides. We also determined the activity of detoxifying enzymes （esterases [ESTs], glutathione S- transferases [GSTs], and mixed-fimction oxidases [MFOs]）. Moderate levels of resistance were detected in the field populations to acephate, thiamethoxam and buprofezin （resistance factors 1.05-20.92 fold, 4.52-14.99 fold, and 1.00-18.09 fold, respectively） as compared with susceptible strain while there were low levels of resistance to imidacloprid （resistance factor 1.23-6.70 fold） and complete sensitivity to etofenoprox （resistance factor 1.05- 1.66 fold）. EST activities in the field populations were 1.06 to 3.09 times higher than the susceptible strain while for GST and MFO the ratios varied from 1.29 to 3.41 and 1.03 to 1.76, respectively. The EST activity was found to be correlated to acephate resistance （r = 0.999, P ≥ 0.001）. The high selection pressure of organophosphate, neonicotinoid, and insect growth regulator （IGR） in the field is likely to be contributing for resistance in BPH to multiple insecticides, leading to control failures. The results obtained will be beneficial to IPM recommendations for the use of effective insecticides against BPH.展开更多
Biotransformation and detoxification responses to the exposure to five polycyclic aromatic hydrocarbons were investigated in crucian（Carassius auratus）. Juvenile crucian were treated with a single intraperitoneal in...Biotransformation and detoxification responses to the exposure to five polycyclic aromatic hydrocarbons were investigated in crucian（Carassius auratus）. Juvenile crucian were treated with a single intraperitoneal injection of each compound at dosages of 0.1, 1.0, 2.0, 5.0 and 8.0（or 10.0） mg/kg and sacrificed 15 d later to determine 7-ethoxyresorufin-O-deethylase（EROD） and glutathione S-transferases（GST） activities in gill S9 fractions. EROD activity is significantly increased by benzo（b）fluoranthene and indeno（1,2,3-cd）pyrene at all the doses. High dosages of PAHs induced GST activity and the inducing ability of them increased in the following order： fluorene fluorantheneindeno（1,2,3-cd）pyrenebenzo（g,h,i）perylenebenzo（b）fluoranthene. In all the cases, dose dependence appeared to exist. The gill EROD and GST in Carassius auratus are useful biomarkers to estimate sub-acute toxicity of both polycyclic aromatic hydrocarbons（PAHs） and PAHs-like compounds.展开更多
Phenolamide(PA)metabolites play important roles in the interaction between plants and pathogens.The putrescine hydroxycinnamoyl transferase genes Os PHT3 and Os PHT4 positively regulate rice cell death and resistance ...Phenolamide(PA)metabolites play important roles in the interaction between plants and pathogens.The putrescine hydroxycinnamoyl transferase genes Os PHT3 and Os PHT4 positively regulate rice cell death and resistance to Magnaporthe oryzae.The b ZIP transcription factor APIP5,a negative regulator of cell death and rice immunity,directly binds to the Os PHT4 promoter to regulate putrescine-derived PAs.Whether other hydroxycinnamoyl transferase(HT)genes also participate in APIP5-mediated immunity remains unclear.Surprisingly,we find that genes encoding agmatine hydroxycinnamoyl transferases Os AHT1 and Os AHT2,tryptamine hydroxycinnamoyl transferases Os TBT1 and Os TBT2,and tyramine hydroxycinnamoyl transferases Os THT1 and Os THT2,responsible for the biosynthesis of polyamine-derived PAs are all up-regulated in APIP5-RNAi transgenic plants compared with segregated wild-type rice.Furthermore,both Os AHT1/2 and Os TBT1/2 are induced during M.oryzae infection,showing expression patterns similar to those previously reported for Os THT1/2 and Os PHT3/4.Transgenic plants overexpressing either Os AHT2-GFP or Os TBT1-GFP show enhanced resistance against M.oryzae and accumulated more PA metabolites and lignin compared with wild-type plants.Interestingly,as demonstrated for Os PHT4,APIP5 directly binds to the promoters of Os AHT1/2,Os TBT1/2,and Os THT1/2,repressing their transcription.Together,these results indicate that the HT genes are common targets of APIP5 and that PAs play critical roles in rice immunity.展开更多
Micromelalopha troglodyta （Graeser） is an important pest of poplar in China. Glutathione S-transferases （GSTs） are known to be responsible for adaptation mechanisms of M. troglodyta. The activities and kinetic con...Micromelalopha troglodyta （Graeser） is an important pest of poplar in China. Glutathione S-transferases （GSTs） are known to be responsible for adaptation mechanisms of M. troglodyta. The activities and kinetic constants of glutathione S-transferases in M. troglodyta were studied. Significant differences in glutathione S-transferase activity and kinetic characteristics were observed among five instars of M. troglodyta larvae. Furthermore, the inhibition of glutathione S-transferase activity in five instars by 24 inhibitors was conducted. The results show the inhibition of GST activity of different instars by 24 inhibitors was different. For GST activity in the 1st instar, chlorpyrifos, lambda-cyhalothrin, endosulfan, abamectin, fipronil and pyridaben were the best inhibitors tested, and for GST activity in the 2nd instar, tannic acid and quercetin were the most potent inhibitors tested, and for GST activity in the 3rd instar, the inhibitory effects of quercetin, chlorpyrifos and lambda-cyhalothrin were the highest, and for GST activity in the 4th instar, quercetin and lambda-cyhalothrin were the best inhibitors, and the inhibitory effect of phoxim was the highest for GST activity in the 5th instar. Our results show that glutathione S-transferases in different instars are qualitatively different in isozyme composition and thus different in sensitivity to inhibitors.展开更多
5-Aminolevulinic acid （ALA）, a major photosensitivity insecticide, has attracted increasing attention as a new type of highly efficient, environmental friendly pesticide to be used to control the pest. To examine wh...5-Aminolevulinic acid （ALA）, a major photosensitivity insecticide, has attracted increasing attention as a new type of highly efficient, environmental friendly pesticide to be used to control the pest. To examine whether or not ALA acts effectively to grasshopper, Oxya chinensis and elucidate the detoxification mechanism of ALA, the susceptibility to ALA was assessed in O. chinensis and two major metabolic detoxification enzymes including glutathione S-transferases （GSTs） and general esterases （ESTs）-specific activities were compared in different development stages and different body sections of O. chinensis treated by ALA and the control. The results showed that the ALA exhibited obvious toxicity to the grasshopper in different development stages. In the low-dose treatment （0.0597 mmol L-1）, the mortalities of O. chinensis reached a significant level （55.5% in the 1st instar nymphs, 61.4% in the 2nd instar nymphs, 71.4% in the 3rd instar nymphs, and 64.4% in the 4th instar nymphs. But, there was no dose-dependent toxic effect. Thereby, we proposed that ALA has the potential for acting as photosensitivity insecticide for controlling O. chinensis. GSTs activity assays using CDNB and DCNB as substrates indicated that the thorax and abdomen of the different instar nymphs treated by ALA showed 1.52-5.56 fold significantly increased GSTs activities compared with the control. However, for the ESTs-specific activity assay, there was no significant difference between O. chinensis treated by ALA and the control within different instar nymphs, when a-NA, a-NB and b-NA were used as substrates. Therefore, GSTs-mediated metabolic detoxification as evidenced by significantly increased GSTs activities might contribute to protect against oxidative damage and oxidative stress by ALA in O. chinensis.展开更多
Clonostachys rosea (C. rosea) is a biocontrol agent that is used to combat and prevent phytopathogenic fungi attacks because of its ability to involve many factors and diverse modes of action. The reactions of C. rose...Clonostachys rosea (C. rosea) is a biocontrol agent that is used to combat and prevent phytopathogenic fungi attacks because of its ability to involve many factors and diverse modes of action. The reactions of C. rosea on the control of gray mold disease in tomato leaves were investigated in this study. To investigate the reactions of C. rosea in inducing resistance to tomato plants, three treatments, including Botrytis cinerea treatment (treatment B), C. rosea treatment (treatment C), C. rosea and B. cinerea treatment (treatment C + B) and water (control), to be applied on tomato leaves were set up. Disease severity was subsequently evaluated and compared with the control. The treatment of tomato leaves with C. rosea (15 μg/ml) significantly reduced the disease index after inoculation and severity of gray mold caused by Botrytis cinerea. The results indicated that the C. rosea treatment stimulated the activity of the defense related enzymes: Peroxidases (POX), lipoxygenases (LOX) and glutathione S-transferases (GST), and the treatment C + B reduced the incidence and severity of the gray mold. Furthermore, C. rosea treatment increased the activity of pathogenesis related proteins PR1. Therefore, our results suggest that C. rosea could enhance the resistance of tomato plants to gray mold through the activation of defense genes and via the enhancement of defense-related enzymatic activities.展开更多
Objective To investigate the associations of genetic polymorphisms in GSTs genes of the Hakka population of south China with family histories of certain chronic diseases.Methods Five hundred and thirty‐nine healthy H...Objective To investigate the associations of genetic polymorphisms in GSTs genes of the Hakka population of south China with family histories of certain chronic diseases.Methods Five hundred and thirty‐nine healthy Hakka natives of Meizhou city of Guangdong province in south China were involved.The genotypes of GSTM1,GSTT1,GSTP1,GSTM3,and GSTA1 were determined using PCR and restriction fragment length polymorphism analysis.The observed polymorphisms were analyzed by Chi‐square and Hardy‐Weinberg equilibrium tests.Logistic regression analysis was used to determine the associations of the distributions of GST genotypes with family history of certain chronic diseases.Results The distributions of polymorphisms in GSTP1,GSTM3,and GSTA1 conformed to the Hardy‐Weinberg equilibrium.Compared to the Cantonese,the Hakka had a lower distribution of the GSTM3 deletion genotype （3.15% vs.11.9%）.A weak association was observed between the GSTM1 genetic polymorphism and family history of hypertension.Alcohol drinkers had a higher frequency of the null‐GSTM1 genotype,while smokers had a higher frequency of a variant GSTP1 genotype.Conclusion The results suggest that the Hakka is a special and distinctive Han Chinese ethnic group with different GSTs genetic polymorphisms.Smoking and drinking might be related to the distribution of GST genotypes.展开更多
The melon aphid, <i>Aphis gossypii</i> Glover (Hemiptera: Aphididae), is a highly polyphagous sap sucking pest on wide varieties of crops including cotton and vegetables. It is a notorious vector of many p...The melon aphid, <i>Aphis gossypii</i> Glover (Hemiptera: Aphididae), is a highly polyphagous sap sucking pest on wide varieties of crops including cotton and vegetables. It is a notorious vector of many plant viruses that are persistently and non-persistently transmitted. In nature, aphids are regulated by their natural enemies. However, chemical control remains a major management tool even though resistance to insecticides has been documented worldwide. A better understanding of mechanisms by which insecticide resistance occurs and its early detection is desirable to develop effective management strategies. The present investigation was conducted to study the development of resistance to an organophosphate (OP) compound-dimethoate, identify biochemical mechanism(s) involved in resistance and study cross-resistance to imidacloprid in laboratory selected <i>A. gossypii</i> strains in comparison to susceptible strains. Bioassay studies revealed that the LC50 values increased dramatically with dimethoate selection in resistant strains and the resistance ratio (RR) was 270-, 243- and 210-fold greater than that of the susceptible strains by 30th generation. Further, biochemical assays revealed enhanced activities of carboxylesterases (CarE), glutathione S-transferases (GSTs) and cytochrome P450-mediated <i>p</i>-Nitroanisole <i>O</i>-demethylase (PNOD) in resistant strains supporting their role in dimethoate detoxification. This study thus revealed that enhanced activity of detoxifying enzymes <i>viz</i>., CarE, GSTs and PNODs is one of the mechanisms underlying dimethoate resistance in <i>A. gossypii</i> collected from South India. Interestingly, the possibility of negatively correlated cross-resistance to imidacloprid was identified in three OP- resistant strains exhibiting 2.97-, 2.56- and 3.76-fold sensitivity to imidacloprid (a novel neonicotinoid). This indicated that the latter was less affected by the resistance mechanism(s) present.展开更多
The melon aphid, Aphis gossypii Glover (Hemiptera: Aphididae), is a highly polyphagous sap sucking pest on wide varieties of crops including cotton and vegetables. It is a notorious vector of many plant viruses that a...The melon aphid, Aphis gossypii Glover (Hemiptera: Aphididae), is a highly polyphagous sap sucking pest on wide varieties of crops including cotton and vegetables. It is a notorious vector of many plant viruses that are persistently and non-persistently transmitted. In nature, aphids are regulated by their natural enemies. However, chemical control remains a major management tool even though resistance to insecticides has been documented worldwide. A better understanding of mechanisms by which insecticide resistance occurs and its early detection is desirable to develop effective management strategies. The present investigation was conducted to study the development of resistance to an organophosphate (OP) compound-dimethoate, identify biochemical mechanism(s) involved in resistance and study cross-resistance to imidacloprid in laboratory selected A. gossypii strains in comparison to susceptible strains. Bioassay studies revealed that the LC50 values increased dramatically with dimethoate selection in resistant strains and the resistance ratio (RR) was 270-, 243- and 210-fold greater than that of the susceptible strains by 30th generation. Further, biochemical assays revealed enhanced activities of carboxylesterases (CarE), glutathione S-transferases (GSTs) and cytochrome P450-mediated p-Nitroanisole O-demethylase (PNOD) in resistant strains supporting their role in dimethoate detoxification. This study thus revealed that enhanced activity of detoxifying enzymes viz., CarE, GSTs and PNODs is one of the mechanisms underlying dimethoate resistance in A. gossypii collected from South India. Interestingly, the possibility of negatively correlated cross-resistance to imidacloprid was identified in three OP- resistant strains exhibiting 2.97-, 2.56- and 3.76-fold sensitivity to imidacloprid (a novel neonicotinoid). This indicated that the latter was less affected by the resistance mechanism(s) present.展开更多
基金the National Natural Science Foundation of China,No.39660021
文摘AIM To investigate the effect of Boschniakiarossica（BR）extract on expression of GST-P,p53 and p21<sup>ras</sup>proteins in early stage of chemicalhepatocarcinogenesis in rats and its anti-inflammatory activities.METHODS The expression of tumor marker-placental form glutathione S-transferase（GST-P）,p53 and p21<sup>ras</sup>proteins were investigated byimmunohistochemical techniques and ABCmethod.Anti-inflammatory activities of BR werestudied by xylene and croton oil-induced mouseear edema,carrageenin,histamine and hotscald-induced rat pow edema,adjuvant-inducedrat arthritis and cotton pellet-induced mousegranuloma formation methods.RESULTS The 500 mg/kg of BR-H<sub>2</sub>O extractfractionated from BR-Methanol extract hadinhibitory effect on the formation of DEN-inducedGST-P-positive foci in rat liver（GST-P stainingwas 78% positive in DEN+AAF group vs 20%positive in DEN+AAF+BR group,P【0.05）andthe expression of mutant p53 and p21<sup>ras</sup>proteinwas lower than that of hepatic preneoplasticlesions（33% and 22% positive respectively inDEN+AAF group vs negative in DEN+AAF+BRgroup）.Both CH<sub>2</sub>Cl<sub>2</sub> and H<sub>2</sub>O extracts from BRhad anti-inflamatory effect in xylene and crotonoil-induced mouse ear edema（inhibitory rateswere 26%-29% and 35%-59%,respectively）. BR-H<sub>2</sub>O extract exhibited inhibitory effect incarrageenin,histamine and hot scald-inducedhind paw edema and adjuvant-induced arthritis inrats and cotton pellet-induced granulomaformation in mice.CONCLUSION BR extract exhibited inhibitory effect on formation of preneoplastic hepatic foci in early stage of rat chemical hepato-carcinogenesis. Both CH<sub>2</sub>CI<sub>2</sub> and H<sub>2</sub>O extracts from BR exerted anti-inflammatory effect in rats and mice.
基金supported by grants from the National Natural Science Foundation of China (30901943)the Program for New Century Excellent Talents in University (NCET-04-0437)+1 种基金the E-institute of Shanghai Municipal Education Commission (E03008)the Innovative Research Team in Universities of Shanghai Municipal Education Commission
文摘BACKGROUND: Enzymes involved in drug and xenobiotic metabolism have been considered to exist in two groups: phase I and phase II enzymes. Cytochrome P450 isoenzymes (CYPs) are the most important phase I enzymes in the metabolism of xenobiotics. The products of phase I metabolism are then acted upon by phase II enzymes, including glutathione S-transferases (GSTs). Herbs that inhibit CYPs such as CYP3A4 or that induce GSTs may have the potential to protect against chemical carcinogenesis since the mutagenic effects of carcinogens are often mediated through an excess of CYP-generated reactive intermediates. This study was designed to investigate the effects of salvianolic acid B (Sal B), a pure compound extracted from Radix Salviae Miltiorrhizae, a Chinese herb, on cell proliferation and CYP1A2 and CYP3A4 mRNA expression in the presence or absence of rifampicin, a potent inducer of CYPs and GST protein expression in HepG2 cells. METHODS: HepG2 cells were incubated with different concentrations of Sal B. Cell proliferation was determined by SYTOX-Green nucleic acid staining. CYP3A4 and CYP1A2 mRNA expression was assayed by real-time PCR. GST protein expression was analyzed by Western blotting. RESULTS: Low concentrations of Sal B (0-20 μmol/L) had no significant effects on cell proliferation, while higher concentrations (100-250 μmol/L) significantly inhibited proliferation in a concentration-dependent manner. Ten μmol/L Sal B, but not 1 μmol/L, down-regulated CYP3A4 and CYP1A2 mRNA expression after 24 hours of incubation, whereas both 1 and 10 μmol/L Sal B down-regulated CYP3A4mRNA expression after 96 hours of incubation; moreover, 1 and 10 μmol/L Sal B inhibited CYP3A4 mRNA expression induced by rifampicin. Both 1 μmol/L and 10 μmol/L Sal B increased GST expression. CONCLUSION: Sal B inhibits CYP3A4 and CYP1A2 mRNA expression and induces GST expression in HepG2 cells.
基金Supported by the Scientific and Technological Foundation of the Education Department of Jiangxi Province
文摘AIM：To explore the expressions of GST-π and telomerase activity in esophageal carcinoma and premalignant lesions and to investigate the value of endoscopic methylene blue （MB） and Lugol＇s iodine double staining. METHODS： Seventy-two patients with esophagopathy were sprayed endoscopically with MB and Lugol＇s iodine in proper order and the areas stained blue and brown, and the area between the blue and brown stains were obtained. Depending on the pattern of mucosal staining, biopsy specimen was obtained. GST-π and telomerase activity in specimens were examined by immunohistochemistry and PCR-based silver staining telomeric repeat amplification protocol, respectively. RESULTS： After MB and Lugol＇s iodine staining, the area between both the colors was obtained in 64 of the 72 patients and the areas were stained blue and brown in all of the 72 patients. Association test of two simultaneous ordinal categorical data showed a correlation between the esophageal mucosal staining and the esophageal histology （P〈0.005）. The expression of GST-π and telomerase activity in esophageal carcinoma and premalignant lesions increased. The expression of GST-π and telomerase activity in dysplasia and carcinoma was significantly higher than that in normal epithelium （P〈0.005）. The expression in hyperplasia was slightly higher than that in normal epithelium. With the lesions progressing from low- to moderate- to high-grade dysplasia, the positive rate increased （P〈0.025）. Expression of GST-π was correlated with that of telomerase activity in dysplasia and carcinoma （φ= 0.4831, P〈0.005;φ= 0.3031, P〈0.025, respectively）; but there was no correlation between them in normal epithelium and hyperplasia. CONCLUSION： The expression of GST-π and telomerase may be an early event in the carcinogenesis of esophagus. They may play an induced and synergistic role with each other in the carcinogenesis of esophagus. Endoscopic MB and Lugol＇s iodine double staining and detection of GST-π and telomera
基金Supported by Science project of Hunan Provincial Health Commission,No.B202304089304.
文摘Breast cancer is the most common malignancy in women worldwide.Triplenegative breast cancer(TNBC),refers breast cancer negative for estrogen receptor,progesterone receptor and human epidermal growth factor receptor 2,characterized by high drug resistance,high metastasis and high recurrence,treatment of which is a difficult problem in the clinical treatment of breast cancer.In order to better treat TNBC clinically,it is a very urgent task to explore the mechanism of TNBC resistance in basic breast cancer research.Pregnane X receptor(PXR)is a nuclear receptor whose main biological function is to participate in the metabolism,transport and clearance of allobiological agents in PXR.PXR plays an important role in drug metabolism and clearance,and PXR is highly expressed in tumor tissues of TNBC patients,which is related to the prognosis of breast cancer patients.This reviews synthesized the important role of PXR in the process of high drug resistance to TNBC chemotherapeutic drugs and related research progress.
文摘The brown planthopper （BPH）, Nilaparvata lugens （Stal）, is one of the major pests of rice throughout Asia. Extensive use of insecticides for suppressing N. lugens has resulted in the development of insecticide resistance leading to frequent control failures in the field. The aim of the present study was to evaluate resistance in the field populations of N. lugens from major rice growing states of South India to various insecticides. We also determined the activity of detoxifying enzymes （esterases [ESTs], glutathione S- transferases [GSTs], and mixed-fimction oxidases [MFOs]）. Moderate levels of resistance were detected in the field populations to acephate, thiamethoxam and buprofezin （resistance factors 1.05-20.92 fold, 4.52-14.99 fold, and 1.00-18.09 fold, respectively） as compared with susceptible strain while there were low levels of resistance to imidacloprid （resistance factor 1.23-6.70 fold） and complete sensitivity to etofenoprox （resistance factor 1.05- 1.66 fold）. EST activities in the field populations were 1.06 to 3.09 times higher than the susceptible strain while for GST and MFO the ratios varied from 1.29 to 3.41 and 1.03 to 1.76, respectively. The EST activity was found to be correlated to acephate resistance （r = 0.999, P ≥ 0.001）. The high selection pressure of organophosphate, neonicotinoid, and insect growth regulator （IGR） in the field is likely to be contributing for resistance in BPH to multiple insecticides, leading to control failures. The results obtained will be beneficial to IPM recommendations for the use of effective insecticides against BPH.
基金Supported by the National Natural Science Foundation of China(No.51079049)the Crucial Special Project of National Water Pollution Control and Management Science of China(No.2008ZX07421-002)
文摘Biotransformation and detoxification responses to the exposure to five polycyclic aromatic hydrocarbons were investigated in crucian（Carassius auratus）. Juvenile crucian were treated with a single intraperitoneal injection of each compound at dosages of 0.1, 1.0, 2.0, 5.0 and 8.0（or 10.0） mg/kg and sacrificed 15 d later to determine 7-ethoxyresorufin-O-deethylase（EROD） and glutathione S-transferases（GST） activities in gill S9 fractions. EROD activity is significantly increased by benzo（b）fluoranthene and indeno（1,2,3-cd）pyrene at all the doses. High dosages of PAHs induced GST activity and the inducing ability of them increased in the following order： fluorene fluorantheneindeno（1,2,3-cd）pyrenebenzo（g,h,i）perylenebenzo（b）fluoranthene. In all the cases, dose dependence appeared to exist. The gill EROD and GST in Carassius auratus are useful biomarkers to estimate sub-acute toxicity of both polycyclic aromatic hydrocarbons（PAHs） and PAHs-like compounds.
基金supported by grants from the National Natural Science Foundation of China (32161143009, 31822041 and 31972225) to Y.N.the National Natural Science Foundation of China (U20A2021) to R.W.the National Natural Science Foundation of China (31801692) to F.Z
文摘Phenolamide(PA)metabolites play important roles in the interaction between plants and pathogens.The putrescine hydroxycinnamoyl transferase genes Os PHT3 and Os PHT4 positively regulate rice cell death and resistance to Magnaporthe oryzae.The b ZIP transcription factor APIP5,a negative regulator of cell death and rice immunity,directly binds to the Os PHT4 promoter to regulate putrescine-derived PAs.Whether other hydroxycinnamoyl transferase(HT)genes also participate in APIP5-mediated immunity remains unclear.Surprisingly,we find that genes encoding agmatine hydroxycinnamoyl transferases Os AHT1 and Os AHT2,tryptamine hydroxycinnamoyl transferases Os TBT1 and Os TBT2,and tyramine hydroxycinnamoyl transferases Os THT1 and Os THT2,responsible for the biosynthesis of polyamine-derived PAs are all up-regulated in APIP5-RNAi transgenic plants compared with segregated wild-type rice.Furthermore,both Os AHT1/2 and Os TBT1/2 are induced during M.oryzae infection,showing expression patterns similar to those previously reported for Os THT1/2 and Os PHT3/4.Transgenic plants overexpressing either Os AHT2-GFP or Os TBT1-GFP show enhanced resistance against M.oryzae and accumulated more PA metabolites and lignin compared with wild-type plants.Interestingly,as demonstrated for Os PHT4,APIP5 directly binds to the promoters of Os AHT1/2,Os TBT1/2,and Os THT1/2,repressing their transcription.Together,these results indicate that the HT genes are common targets of APIP5 and that PAs play critical roles in rice immunity.
基金supported by National Natural Science Foundation of China(Contract No.30600476 and 30972376)
文摘Micromelalopha troglodyta （Graeser） is an important pest of poplar in China. Glutathione S-transferases （GSTs） are known to be responsible for adaptation mechanisms of M. troglodyta. The activities and kinetic constants of glutathione S-transferases in M. troglodyta were studied. Significant differences in glutathione S-transferase activity and kinetic characteristics were observed among five instars of M. troglodyta larvae. Furthermore, the inhibition of glutathione S-transferase activity in five instars by 24 inhibitors was conducted. The results show the inhibition of GST activity of different instars by 24 inhibitors was different. For GST activity in the 1st instar, chlorpyrifos, lambda-cyhalothrin, endosulfan, abamectin, fipronil and pyridaben were the best inhibitors tested, and for GST activity in the 2nd instar, tannic acid and quercetin were the most potent inhibitors tested, and for GST activity in the 3rd instar, the inhibitory effects of quercetin, chlorpyrifos and lambda-cyhalothrin were the highest, and for GST activity in the 4th instar, quercetin and lambda-cyhalothrin were the best inhibitors, and the inhibitory effect of phoxim was the highest for GST activity in the 5th instar. Our results show that glutathione S-transferases in different instars are qualitatively different in isozyme composition and thus different in sensitivity to inhibitors.
基金supported by the National Natural Science Foundation of China (30870302 and 30970410)the Youth Foundation of Shanxi Province, China (2007021030)the Research Fund for the Doctoral Program of Higher Education of China (20101401120008)
文摘5-Aminolevulinic acid （ALA）, a major photosensitivity insecticide, has attracted increasing attention as a new type of highly efficient, environmental friendly pesticide to be used to control the pest. To examine whether or not ALA acts effectively to grasshopper, Oxya chinensis and elucidate the detoxification mechanism of ALA, the susceptibility to ALA was assessed in O. chinensis and two major metabolic detoxification enzymes including glutathione S-transferases （GSTs） and general esterases （ESTs）-specific activities were compared in different development stages and different body sections of O. chinensis treated by ALA and the control. The results showed that the ALA exhibited obvious toxicity to the grasshopper in different development stages. In the low-dose treatment （0.0597 mmol L-1）, the mortalities of O. chinensis reached a significant level （55.5% in the 1st instar nymphs, 61.4% in the 2nd instar nymphs, 71.4% in the 3rd instar nymphs, and 64.4% in the 4th instar nymphs. But, there was no dose-dependent toxic effect. Thereby, we proposed that ALA has the potential for acting as photosensitivity insecticide for controlling O. chinensis. GSTs activity assays using CDNB and DCNB as substrates indicated that the thorax and abdomen of the different instar nymphs treated by ALA showed 1.52-5.56 fold significantly increased GSTs activities compared with the control. However, for the ESTs-specific activity assay, there was no significant difference between O. chinensis treated by ALA and the control within different instar nymphs, when a-NA, a-NB and b-NA were used as substrates. Therefore, GSTs-mediated metabolic detoxification as evidenced by significantly increased GSTs activities might contribute to protect against oxidative damage and oxidative stress by ALA in O. chinensis.
文摘Clonostachys rosea (C. rosea) is a biocontrol agent that is used to combat and prevent phytopathogenic fungi attacks because of its ability to involve many factors and diverse modes of action. The reactions of C. rosea on the control of gray mold disease in tomato leaves were investigated in this study. To investigate the reactions of C. rosea in inducing resistance to tomato plants, three treatments, including Botrytis cinerea treatment (treatment B), C. rosea treatment (treatment C), C. rosea and B. cinerea treatment (treatment C + B) and water (control), to be applied on tomato leaves were set up. Disease severity was subsequently evaluated and compared with the control. The treatment of tomato leaves with C. rosea (15 μg/ml) significantly reduced the disease index after inoculation and severity of gray mold caused by Botrytis cinerea. The results indicated that the C. rosea treatment stimulated the activity of the defense related enzymes: Peroxidases (POX), lipoxygenases (LOX) and glutathione S-transferases (GST), and the treatment C + B reduced the incidence and severity of the gray mold. Furthermore, C. rosea treatment increased the activity of pathogenesis related proteins PR1. Therefore, our results suggest that C. rosea could enhance the resistance of tomato plants to gray mold through the activation of defense genes and via the enhancement of defense-related enzymatic activities.
基金supported by grants from the Team Project of Guangdong Province National Science Fund (NO.015042)the Research Fund of Center for Disease Control and Prevention of Guangdong (GDCDC) Province, China
文摘Objective To investigate the associations of genetic polymorphisms in GSTs genes of the Hakka population of south China with family histories of certain chronic diseases.Methods Five hundred and thirty‐nine healthy Hakka natives of Meizhou city of Guangdong province in south China were involved.The genotypes of GSTM1,GSTT1,GSTP1,GSTM3,and GSTA1 were determined using PCR and restriction fragment length polymorphism analysis.The observed polymorphisms were analyzed by Chi‐square and Hardy‐Weinberg equilibrium tests.Logistic regression analysis was used to determine the associations of the distributions of GST genotypes with family history of certain chronic diseases.Results The distributions of polymorphisms in GSTP1,GSTM3,and GSTA1 conformed to the Hardy‐Weinberg equilibrium.Compared to the Cantonese,the Hakka had a lower distribution of the GSTM3 deletion genotype （3.15% vs.11.9%）.A weak association was observed between the GSTM1 genetic polymorphism and family history of hypertension.Alcohol drinkers had a higher frequency of the null‐GSTM1 genotype,while smokers had a higher frequency of a variant GSTP1 genotype.Conclusion The results suggest that the Hakka is a special and distinctive Han Chinese ethnic group with different GSTs genetic polymorphisms.Smoking and drinking might be related to the distribution of GST genotypes.
文摘The melon aphid, <i>Aphis gossypii</i> Glover (Hemiptera: Aphididae), is a highly polyphagous sap sucking pest on wide varieties of crops including cotton and vegetables. It is a notorious vector of many plant viruses that are persistently and non-persistently transmitted. In nature, aphids are regulated by their natural enemies. However, chemical control remains a major management tool even though resistance to insecticides has been documented worldwide. A better understanding of mechanisms by which insecticide resistance occurs and its early detection is desirable to develop effective management strategies. The present investigation was conducted to study the development of resistance to an organophosphate (OP) compound-dimethoate, identify biochemical mechanism(s) involved in resistance and study cross-resistance to imidacloprid in laboratory selected <i>A. gossypii</i> strains in comparison to susceptible strains. Bioassay studies revealed that the LC50 values increased dramatically with dimethoate selection in resistant strains and the resistance ratio (RR) was 270-, 243- and 210-fold greater than that of the susceptible strains by 30th generation. Further, biochemical assays revealed enhanced activities of carboxylesterases (CarE), glutathione S-transferases (GSTs) and cytochrome P450-mediated <i>p</i>-Nitroanisole <i>O</i>-demethylase (PNOD) in resistant strains supporting their role in dimethoate detoxification. This study thus revealed that enhanced activity of detoxifying enzymes <i>viz</i>., CarE, GSTs and PNODs is one of the mechanisms underlying dimethoate resistance in <i>A. gossypii</i> collected from South India. Interestingly, the possibility of negatively correlated cross-resistance to imidacloprid was identified in three OP- resistant strains exhibiting 2.97-, 2.56- and 3.76-fold sensitivity to imidacloprid (a novel neonicotinoid). This indicated that the latter was less affected by the resistance mechanism(s) present.
文摘The melon aphid, Aphis gossypii Glover (Hemiptera: Aphididae), is a highly polyphagous sap sucking pest on wide varieties of crops including cotton and vegetables. It is a notorious vector of many plant viruses that are persistently and non-persistently transmitted. In nature, aphids are regulated by their natural enemies. However, chemical control remains a major management tool even though resistance to insecticides has been documented worldwide. A better understanding of mechanisms by which insecticide resistance occurs and its early detection is desirable to develop effective management strategies. The present investigation was conducted to study the development of resistance to an organophosphate (OP) compound-dimethoate, identify biochemical mechanism(s) involved in resistance and study cross-resistance to imidacloprid in laboratory selected A. gossypii strains in comparison to susceptible strains. Bioassay studies revealed that the LC50 values increased dramatically with dimethoate selection in resistant strains and the resistance ratio (RR) was 270-, 243- and 210-fold greater than that of the susceptible strains by 30th generation. Further, biochemical assays revealed enhanced activities of carboxylesterases (CarE), glutathione S-transferases (GSTs) and cytochrome P450-mediated p-Nitroanisole O-demethylase (PNOD) in resistant strains supporting their role in dimethoate detoxification. This study thus revealed that enhanced activity of detoxifying enzymes viz., CarE, GSTs and PNODs is one of the mechanisms underlying dimethoate resistance in A. gossypii collected from South India. Interestingly, the possibility of negatively correlated cross-resistance to imidacloprid was identified in three OP- resistant strains exhibiting 2.97-, 2.56- and 3.76-fold sensitivity to imidacloprid (a novel neonicotinoid). This indicated that the latter was less affected by the resistance mechanism(s) present.
