Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.biocel.2008.09.028
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. 
Clement, M.-V. 
Pervaiz, S. 
Keywords: AP2
Caspase
H2O2
NHE-1
Resveratrol
Issue Date: 2009
Source: 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. https://doi.org/10.1016/j.biocel.2008.09.028
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
URI: http://scholarbank.nus.edu.sg/handle/10635/28914
ISSN: 13572725
DOI: 10.1016/j.biocel.2008.09.028
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

13
checked on Dec 7, 2017

WEB OF SCIENCETM
Citations

14
checked on Nov 23, 2017

Page view(s)

131
checked on Dec 11, 2017

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.