The effects of nicotinamide adenine dinucleotide phosphate （NADPH） oxidase inhibitor apocynin on the enhanced hypoxia induced factor-let （HIF-lct） and endothelin-1 （ET-1） expression, elevated systolic blood pres...The effects of nicotinamide adenine dinucleotide phosphate （NADPH） oxidase inhibitor apocynin on the enhanced hypoxia induced factor-let （HIF-lct） and endothelin-1 （ET-1） expression, elevated systolic blood pressure under chronic intermittent hypoxia （CIH） condition and its action mechanism were investigated. Thirty healthy 8-week old Sprague-Dawley （SD） male rats were randomly divided into three groups （n=10 each）： sham group, CIH group, and apocynin-treated CIH group. Tail artery systolic blood pressure was measured by tail-cuff method. Real-time fluorescence quantitative polymerase chain reaction （PCR） was used to detect the mRNA expression of HIF-lu and ET-1 in the carotid body, and the HIF-1a protein expression was examined by using Western blotting. The levels of malondialdehyde （MDA） and superoxide dismutase （SOD） were determined by using colorimetric method. In addition, the plasma ET-1 and HIF-1a levels were measured by using enzyme-linked immunosorbent assay. It was found that CIH exposure was associated with increased MDA levels, and apo- cynin-treated CIH animals showed reduction in MDA levels. Apocynin treatment prevented CIH-induced hypertension as well as CIH-induced decrease in SOD. The increases of HIF-1a and ET-1 mRNA along with HIF-la protein expression in the carotid body, and elevated circulating HIF-1a and ET-1 levels were observed in CIH-exposed animals. Treatment with apocynin significantly decreased the ET-1 mRNA, HIF-lct protein expression and circulating HIF-la level in CIH-exposed animals, and there was no statistically significant difference in the HIF-lu mRNA expression between CIH group and apo- cynin-treated group. These results indicated that apocynin alleviated CIH-induced hypertension by inhibiting NADPH oxidase, further leading to the reduced vasoconstrictor ET-1 level and oxidative stress. HIF-1a/ET-1 system signal pathway may interact with CIH-induced NADPH oxidase-dependent oxidative stress. Inhibition of NADPH oxidase activity may hopef展开更多
Breast cancer usually grows very quickly,becoming insensitive to blood flow in nearby veins;because of that,inside solid tumors it's possible to find a hypoxic environment,in other words,an environment where oxyge...Breast cancer usually grows very quickly,becoming insensitive to blood flow in nearby veins;because of that,inside solid tumors it's possible to find a hypoxic environment,in other words,an environment where oxygen is less available.Another feature of cancer is its angiogenesis rate,because of the high energy demand,new blood vessels must be produced to take nutrients inside the solid tumor mass.Even with normal blood flow bringing the cancer oxygen and nutrients,its cells favor hypoxia,in an event known as Warburg Effect.According to the Warburg Effect,cells,even with normal oxygen rates,prefer to use fermentation instead of the citric acid cycle to produce ATP.For the cancer to operate normally in hypoxia,a transcription factor family is activated,known as hypoxia-induced factors(HIF),composed of a HIF-1βand a HIF-1αsubunits.As HIF-1αis expressed during hypoxia,it is a great target for treatments and a breast cancer biomarker.Because of the role of HIF-1αin cancer and the high incidence of breast cancer worlwide,this review was performed in order to bring the most recent results concerning the role HIF-1αcan exert in breast cancer development and progression.展开更多
Objective: To study the correlation of the change of hypoxia-induced factor-1α (HIF-1α) in oral squamous cell carcinoma lesion with lymph node metastasis and malignant biological molecule expression. Methods: The pa...Objective: To study the correlation of the change of hypoxia-induced factor-1α (HIF-1α) in oral squamous cell carcinoma lesion with lymph node metastasis and malignant biological molecule expression. Methods: The patients with oral squamous cell carcinoma who underwent surgical resection in the First Hospital of Yulin between March 2012 and December 2017 were selected as the research subjects, and right amount of oral squamous cell carcinoma lesion and lesion adjacent to carcinoma were collected after surgical resection to determine the mRNA expression of HIF-1α, proliferation genes and invasion genes as well as the contents of angiogenesis molecules. Results: HIF-1α, PCNA, CDK4, CDK6, Slug, β-catenin and MMP9 mRNA expression as well as VEGF, Ang-2, bFGF and COX-2 contents in oral squamous cell carcinoma lesions were significantly higher than those in adjacent lesions whereas PDCD5, Smac, E-cadherin and RECK mRNA expression were significantly lower than those in adjacent lesions;Pearson correlation analysis showed that HIF-1α mRNA expression in oral squamous cell carcinoma lesions was positively correlated with PCNA, CDK4, CDK6, Slug, β-catenin and MMP9 mRNA expression as well as VEGF, Ang-2, bFGF and COX-2 contents, and negatively correlated with PDCD5, Smac, E-cadherin and RECK mRNA expression. Conclusion: Highly expressed HIF-1α in oral squamous cell carcinoma can promote the proliferation and invasion of cancer cells as well as the angiogenesis in the lesion.展开更多
Objective： To investigate whether ginsenoside-Rbl （Gs-Rb1） inhibits the apoptosis of hypoxia cardiomyocytes by up-regulating apelin-APJ system and whether the system is affected by hypoxia-induced factor 1α （Hif-...Objective： To investigate whether ginsenoside-Rbl （Gs-Rb1） inhibits the apoptosis of hypoxia cardiomyocytes by up-regulating apelin-APJ system and whether the system is affected by hypoxia-induced factor 1α （Hif-1α）. Methods： Neonatal rat cardiomyocytes were randomly divided into 6 groups： a control group, a simple COCl2 group, a simple Gs-Rbl group, a CoCl2 and Gs-Rbl hypoxia group, a CoCl2 and 3-（5＇-hydroxymethyl-2＇-furyl）-1-benzylindazole （YC-1） group, a CoCl2 and YC-1 group and a Gs-Rbl group, in which YC-1 inhibits the synthesis and accelerates the degradation of Hif-la. The concentration of COCI2, Gs-Rbl and YC-1 was 500 μmol/L, 200 μ mol/L and 5 μmol/L, respectively; the apoptosis ratio was analyzed with a flow cytometer; and apelin, APJ and Hif-1 c= were assayed with immunocytochemistry, Western blot assays and reverse transcription polymerase chain reaction （RT-PCR）. Results： （1） The anti-apoptosis effect of Gs-Rbl on hypoxia cardiomyocytes was significantly inhibited by YC-1; （2） Hypoxia significantly up-graded the expression of mRNA and protein of apelin; this effect was further reinforced by Gs-Rbl and significantly inhibited by YC-1; （3） Gs-Rb1 further strengthened the expression of APJ mRNA and APJ proteins once hypoxia occurred, which was significantly inhibited by YC-1; （4） Gs-Rb1 significantly increased the expression of Hif-1α, which was completely abolished by YC-1; （5） There was a negative relationship between AR and apelin （or APJ, including mRNA and protein）, a positive correlation between apelin （or APJ） protein and Hif-1a protein, in hypoxia cardiomyocytes. Conclusion： The apelin-APJ system plays an important role in the anti-apoptosis effect of Gs- Rb1 on hypoxia neonatal cardiomyocytes, which was partly adjusted by Hif-1α.展开更多
基金supported by the National Natural Science Foundation of China(No.81070067)
文摘The effects of nicotinamide adenine dinucleotide phosphate （NADPH） oxidase inhibitor apocynin on the enhanced hypoxia induced factor-let （HIF-lct） and endothelin-1 （ET-1） expression, elevated systolic blood pressure under chronic intermittent hypoxia （CIH） condition and its action mechanism were investigated. Thirty healthy 8-week old Sprague-Dawley （SD） male rats were randomly divided into three groups （n=10 each）： sham group, CIH group, and apocynin-treated CIH group. Tail artery systolic blood pressure was measured by tail-cuff method. Real-time fluorescence quantitative polymerase chain reaction （PCR） was used to detect the mRNA expression of HIF-lu and ET-1 in the carotid body, and the HIF-1a protein expression was examined by using Western blotting. The levels of malondialdehyde （MDA） and superoxide dismutase （SOD） were determined by using colorimetric method. In addition, the plasma ET-1 and HIF-1a levels were measured by using enzyme-linked immunosorbent assay. It was found that CIH exposure was associated with increased MDA levels, and apo- cynin-treated CIH animals showed reduction in MDA levels. Apocynin treatment prevented CIH-induced hypertension as well as CIH-induced decrease in SOD. The increases of HIF-1a and ET-1 mRNA along with HIF-la protein expression in the carotid body, and elevated circulating HIF-1a and ET-1 levels were observed in CIH-exposed animals. Treatment with apocynin significantly decreased the ET-1 mRNA, HIF-lct protein expression and circulating HIF-la level in CIH-exposed animals, and there was no statistically significant difference in the HIF-lu mRNA expression between CIH group and apo- cynin-treated group. These results indicated that apocynin alleviated CIH-induced hypertension by inhibiting NADPH oxidase, further leading to the reduced vasoconstrictor ET-1 level and oxidative stress. HIF-1a/ET-1 system signal pathway may interact with CIH-induced NADPH oxidase-dependent oxidative stress. Inhibition of NADPH oxidase activity may hopef
基金FAPESP Grant(2017/03558-3)Fellowship grant CNPq(133505/2018-9)to Carlos HFP.
文摘Breast cancer usually grows very quickly,becoming insensitive to blood flow in nearby veins;because of that,inside solid tumors it's possible to find a hypoxic environment,in other words,an environment where oxygen is less available.Another feature of cancer is its angiogenesis rate,because of the high energy demand,new blood vessels must be produced to take nutrients inside the solid tumor mass.Even with normal blood flow bringing the cancer oxygen and nutrients,its cells favor hypoxia,in an event known as Warburg Effect.According to the Warburg Effect,cells,even with normal oxygen rates,prefer to use fermentation instead of the citric acid cycle to produce ATP.For the cancer to operate normally in hypoxia,a transcription factor family is activated,known as hypoxia-induced factors(HIF),composed of a HIF-1βand a HIF-1αsubunits.As HIF-1αis expressed during hypoxia,it is a great target for treatments and a breast cancer biomarker.Because of the role of HIF-1αin cancer and the high incidence of breast cancer worlwide,this review was performed in order to bring the most recent results concerning the role HIF-1αcan exert in breast cancer development and progression.
文摘Objective: To study the correlation of the change of hypoxia-induced factor-1α (HIF-1α) in oral squamous cell carcinoma lesion with lymph node metastasis and malignant biological molecule expression. Methods: The patients with oral squamous cell carcinoma who underwent surgical resection in the First Hospital of Yulin between March 2012 and December 2017 were selected as the research subjects, and right amount of oral squamous cell carcinoma lesion and lesion adjacent to carcinoma were collected after surgical resection to determine the mRNA expression of HIF-1α, proliferation genes and invasion genes as well as the contents of angiogenesis molecules. Results: HIF-1α, PCNA, CDK4, CDK6, Slug, β-catenin and MMP9 mRNA expression as well as VEGF, Ang-2, bFGF and COX-2 contents in oral squamous cell carcinoma lesions were significantly higher than those in adjacent lesions whereas PDCD5, Smac, E-cadherin and RECK mRNA expression were significantly lower than those in adjacent lesions;Pearson correlation analysis showed that HIF-1α mRNA expression in oral squamous cell carcinoma lesions was positively correlated with PCNA, CDK4, CDK6, Slug, β-catenin and MMP9 mRNA expression as well as VEGF, Ang-2, bFGF and COX-2 contents, and negatively correlated with PDCD5, Smac, E-cadherin and RECK mRNA expression. Conclusion: Highly expressed HIF-1α in oral squamous cell carcinoma can promote the proliferation and invasion of cancer cells as well as the angiogenesis in the lesion.
基金Supported by Liaoning Province Science and Technique Foundation of China(No.201102107)
文摘Objective： To investigate whether ginsenoside-Rbl （Gs-Rb1） inhibits the apoptosis of hypoxia cardiomyocytes by up-regulating apelin-APJ system and whether the system is affected by hypoxia-induced factor 1α （Hif-1α）. Methods： Neonatal rat cardiomyocytes were randomly divided into 6 groups： a control group, a simple COCl2 group, a simple Gs-Rbl group, a CoCl2 and Gs-Rbl hypoxia group, a CoCl2 and 3-（5＇-hydroxymethyl-2＇-furyl）-1-benzylindazole （YC-1） group, a CoCl2 and YC-1 group and a Gs-Rbl group, in which YC-1 inhibits the synthesis and accelerates the degradation of Hif-la. The concentration of COCI2, Gs-Rbl and YC-1 was 500 μmol/L, 200 μ mol/L and 5 μmol/L, respectively; the apoptosis ratio was analyzed with a flow cytometer; and apelin, APJ and Hif-1 c= were assayed with immunocytochemistry, Western blot assays and reverse transcription polymerase chain reaction （RT-PCR）. Results： （1） The anti-apoptosis effect of Gs-Rbl on hypoxia cardiomyocytes was significantly inhibited by YC-1; （2） Hypoxia significantly up-graded the expression of mRNA and protein of apelin; this effect was further reinforced by Gs-Rbl and significantly inhibited by YC-1; （3） Gs-Rb1 further strengthened the expression of APJ mRNA and APJ proteins once hypoxia occurred, which was significantly inhibited by YC-1; （4） Gs-Rb1 significantly increased the expression of Hif-1α, which was completely abolished by YC-1; （5） There was a negative relationship between AR and apelin （or APJ, including mRNA and protein）, a positive correlation between apelin （or APJ） protein and Hif-1a protein, in hypoxia cardiomyocytes. Conclusion： The apelin-APJ system plays an important role in the anti-apoptosis effect of Gs- Rb1 on hypoxia neonatal cardiomyocytes, which was partly adjusted by Hif-1α.
