Repeated exposure to cruciferous allyl nitrile can induce antioxidant and phase 2 detoxification enzymes in various tissues. In the present study, we examined the effect of five days repeated exposure to allyl nitrile...Repeated exposure to cruciferous allyl nitrile can induce antioxidant and phase 2 detoxification enzymes in various tissues. In the present study, we examined the effect of five days repeated exposure to allyl nitrile at subtoxic levels (0 - 400 μmol/kg/day) on the mouse ear. There was an increase in catalase activity in the ear at 100 - 400 μmol/kg/day, while elevated quinone reductase activity was observed at 400 μmol/kg/day only. Next, after repeated allyl nitrile exposure (0 - 400 μmol/kg/day), the skin irritant croton oil was applied to the ear to induce skin acute inflammation (oedema). Compared with the 0 μmol/kg/day group, animals in the 100 and 400 μmol/kg/day pre-treatment groups showed reduced oedematous response to croton oil. The reduced oedematous response was inversely associated with enhanced myeloperoxidase activity used as index of the presence of neutrophils. These data suggest that repeated exposure to allyl nitrile at subtoxic levels contributes to protection against croton oil-induced ear dermatitis, potentially through decreasing reactive oxygen species and through infiltration of neutrophils.展开更多
Our previous studies showed that resveratrol could inhibit the proliferation of vascular smooth muscle cells （VSMCs） and repress mRNA and protein expression of quinone reductase 2 （NQO2）. This study further explor...Our previous studies showed that resveratrol could inhibit the proliferation of vascular smooth muscle cells （VSMCs） and repress mRNA and protein expression of quinone reductase 2 （NQO2）. This study further explored the potential mechanisms whereby resveratrol inhibits the proliferation of rat VSMCs. Lentiviral vectors that incorporated NQO2 small interfering RNA （siRNA） were constructed and transduced into rat VSMCs. The cell proliferation was detected using the bromodeoxyuridine （BrdU） assay. Cultured rat VSMCs were stimulated with angiotensin II and the level of reactive oxygen species （ROS） was measured using a ROS assay kit. A realtime quantitative PCR was used to detect NQO2 mRNA levels. Extracellular signal-regulated kinase （ERK1/2） and NQO2 protein expression were determined by Western blotting analysis. The inhibitory effect of resveratrol （10 and 50 μmol/L） on the proliferation of rat VSMCs in the NQO2 siRNA group was significantly weaker than that in the normal and scrambled siRNA group （P 〈 0.01）. The ROS level in the NQO2 siRNA and resveratrol （50 μmol/L） treatment groups were lower than that in the normal and scrambled siRNA groups （P 〈 0.01 in both）. Compared with the normal and scrambled siRNA group, the phosphorylation of ERK1/2 was significantly decreased in the NQO2 siRNA and resveratrol （50 μmol/L） treatment group （P 〈 0.01 in both）. In conclusion, high concentration of resveratrol inhibits angiotensin II-induced ERK1/2 phosphorylation and subsequent proliferation by down-regulation of NQO2 in cultured rat VSMCs.展开更多
Resveratrol is a dietary polyphenol espoused to have chemopreventive activity against a variety of human cancer types. We first reported that resveratrol significantly decreases the proliferation of both androgen-depe...Resveratrol is a dietary polyphenol espoused to have chemopreventive activity against a variety of human cancer types. We first reported that resveratrol significantly decreases the proliferation of both androgen-dependent and hormone-refractory prostate cancer cells. However, the effects of resveratrol in normal prostate epithelial and stromal cells, particularly with regard to its uptake, subcellular distribution and intracellular targets, have not been investigated. To advance the knowledge on accessibility and cellular disposition of resveratrol in prostate cells, [3H] resveratrol, fractionation of cell extracts into subcellular compartments, Western blot analysis, resveratrol affinity column chromatography and flow cytometry were used to study the uptake and intracellular distribution of resveratrol in normally cultured prostate stromal （PrSCs） and epithelial cells （PrECs）. Pretreatment of both PrSCs and PrECs for 2 days with resveratrol modulated its uptake and selectively increased its distribution to the membrane and organelle compartments. Resveratrol affinity column chromatography studies showed differential expression of a previously identified resveratrol-targeting protein, quinone reductase 2 （QR2）, in PrSCs and PrECs. Flow cytometric analysis comparing resveratrol-treated and untreated PrSCs showed a large decrease in G1-phase and a concomitant increase in S and G2/M-phases of the cell cycle. These results suggest that resveratrol suppresses PrSC proliferation by affecting cell cycle phase distribution, which may involve the participation by QR2.展开更多
文摘Repeated exposure to cruciferous allyl nitrile can induce antioxidant and phase 2 detoxification enzymes in various tissues. In the present study, we examined the effect of five days repeated exposure to allyl nitrile at subtoxic levels (0 - 400 μmol/kg/day) on the mouse ear. There was an increase in catalase activity in the ear at 100 - 400 μmol/kg/day, while elevated quinone reductase activity was observed at 400 μmol/kg/day only. Next, after repeated allyl nitrile exposure (0 - 400 μmol/kg/day), the skin irritant croton oil was applied to the ear to induce skin acute inflammation (oedema). Compared with the 0 μmol/kg/day group, animals in the 100 and 400 μmol/kg/day pre-treatment groups showed reduced oedematous response to croton oil. The reduced oedematous response was inversely associated with enhanced myeloperoxidase activity used as index of the presence of neutrophils. These data suggest that repeated exposure to allyl nitrile at subtoxic levels contributes to protection against croton oil-induced ear dermatitis, potentially through decreasing reactive oxygen species and through infiltration of neutrophils.
基金supported by grants from the National Natural Science Foundation of China (No.30971255)
文摘Our previous studies showed that resveratrol could inhibit the proliferation of vascular smooth muscle cells （VSMCs） and repress mRNA and protein expression of quinone reductase 2 （NQO2）. This study further explored the potential mechanisms whereby resveratrol inhibits the proliferation of rat VSMCs. Lentiviral vectors that incorporated NQO2 small interfering RNA （siRNA） were constructed and transduced into rat VSMCs. The cell proliferation was detected using the bromodeoxyuridine （BrdU） assay. Cultured rat VSMCs were stimulated with angiotensin II and the level of reactive oxygen species （ROS） was measured using a ROS assay kit. A realtime quantitative PCR was used to detect NQO2 mRNA levels. Extracellular signal-regulated kinase （ERK1/2） and NQO2 protein expression were determined by Western blotting analysis. The inhibitory effect of resveratrol （10 and 50 μmol/L） on the proliferation of rat VSMCs in the NQO2 siRNA group was significantly weaker than that in the normal and scrambled siRNA group （P 〈 0.01）. The ROS level in the NQO2 siRNA and resveratrol （50 μmol/L） treatment groups were lower than that in the normal and scrambled siRNA groups （P 〈 0.01 in both）. Compared with the normal and scrambled siRNA group, the phosphorylation of ERK1/2 was significantly decreased in the NQO2 siRNA and resveratrol （50 μmol/L） treatment group （P 〈 0.01 in both）. In conclusion, high concentration of resveratrol inhibits angiotensin II-induced ERK1/2 phosphorylation and subsequent proliferation by down-regulation of NQO2 in cultured rat VSMCs.
文摘Resveratrol is a dietary polyphenol espoused to have chemopreventive activity against a variety of human cancer types. We first reported that resveratrol significantly decreases the proliferation of both androgen-dependent and hormone-refractory prostate cancer cells. However, the effects of resveratrol in normal prostate epithelial and stromal cells, particularly with regard to its uptake, subcellular distribution and intracellular targets, have not been investigated. To advance the knowledge on accessibility and cellular disposition of resveratrol in prostate cells, [3H] resveratrol, fractionation of cell extracts into subcellular compartments, Western blot analysis, resveratrol affinity column chromatography and flow cytometry were used to study the uptake and intracellular distribution of resveratrol in normally cultured prostate stromal （PrSCs） and epithelial cells （PrECs）. Pretreatment of both PrSCs and PrECs for 2 days with resveratrol modulated its uptake and selectively increased its distribution to the membrane and organelle compartments. Resveratrol affinity column chromatography studies showed differential expression of a previously identified resveratrol-targeting protein, quinone reductase 2 （QR2）, in PrSCs and PrECs. Flow cytometric analysis comparing resveratrol-treated and untreated PrSCs showed a large decrease in G1-phase and a concomitant increase in S and G2/M-phases of the cell cycle. These results suggest that resveratrol suppresses PrSC proliferation by affecting cell cycle phase distribution, which may involve the participation by QR2.
