Please use this identifier to cite or link to this item:
|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|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Feb 28, 2018
WEB OF SCIENCETM
checked on Dec 31, 2018
checked on Mar 17, 2019
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.