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|Title:||Resveratrol regulates the expression of NHE-1 by repressing its promoter activity: Critical involvement of intracellular H2O2and caspases 3 and 6 in the absence of cell death|
|Authors:||Jhumka, Z. |
|Citation:||Jhumka, Z., Clement, M.-V., Pervaiz, S. (2009). Resveratrol regulates the expression of NHE-1 by repressing its promoter activity: Critical involvement of intracellular H2O2and caspases 3 and 6 in the absence of cell death. International Journal of Biochemistry and Cell Biology 41 (4) : 945-956. ScholarBank@NUS Repository.|
|Abstract:||Na+/H+ exchanger-1 (NHE-1) overexpression is associated with carcinogenesis and is an attractive target for intervention. We report that the chemopreventive agent resveratrol (RSV) downregulates NHE-1 in a caspase-dependent manner without inducing cell death. Resveratrol triggered early activation of caspase 3 and late activation of caspase 6, which were not inter-dependent. Whereas, caspase 3 activation appeared to be a direct effect of resveratrol, caspase 6 activation was mediated via intracellular hydrogen peroxide production and iron. Moreover, downregulation of NHE-1 expression was a function of resveratrol-induced repression of NHE-1 gene promoter activity. RNAi-mediated silencing of caspase 3 or 6 blocked the effect of resveratrol on NHE-1 expression, however the effect on NHE-1 promoter was observed at different phases of promoter repression with caspase 3 controlling the early phase (4-12 h) and caspase 6 regulating the late phase (12-24 h). Scavenging hydrogen peroxide or iron only reversed the late phase of resveratrol-induced NHE-1 promoter repression. Finally, an AP2 binding region within NHE-1 gene promoter was identified as the target of resveratrol. Collectively, these data could explain the anti-cancer activity of resveratrol in the light of the association of increased NHE-1 expression with carcinogenesis. © 2008 Elsevier Ltd. All rights reserved.|
|Source Title:||International Journal of Biochemistry and Cell Biology|
|Appears in Collections:||Staff Publications|
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