Regulation of 4-hydroxynonenal-mediated signaling by glutathione S-transferases

4-Hydroxynonenal (HNE), one of the major end products of lipid peroxidation, has been shown to be involved in signal transduction and available evidence suggests that it can affect cell cycle events in a concentration-dependent manner. Glutathione S-transferases (GSTs) can modulate the intracellular...

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Published in:Free Radical Biology and Medicine 2004-09, Vol.37 (5), p.607-619
Main Authors: Awasthi, Yogesh C, Yang, Yusong, Tiwari, Narendra K, Patrick, Brad, Sharma, Abha, Li, Jie, Awasthi, Sanjay
Format: Article
Language:English
Subjects:
Aldehydes - pharmacokinetics
Aldehydes - pharmacology
Animals
Apoptosis
Apoptosis - drug effects
Apoptosis - physiology
Cell cycle
Differentiation
Free radicals
Glutathione
Glutathione S-transferases
Glutathione Transferase - drug effects
Glutathione Transferase - metabolism
HNE
Humans
Lipid peroxidation
Oxidative stress
Proliferation
Signal Transduction - drug effects
Signal Transduction - physiology
Transformation
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Summary:4-Hydroxynonenal (HNE), one of the major end products of lipid peroxidation, has been shown to be involved in signal transduction and available evidence suggests that it can affect cell cycle events in a concentration-dependent manner. Glutathione S-transferases (GSTs) can modulate the intracellular concentrations of HNE by affecting its generation during lipid peroxidation by reducing hydroperoxides and also by converting it into a glutathione conjugate. We have recently demonstrated that overexpression of the Alpha class GSTs in cells leads to lower steady-state levels of HNE, and these cells acquire resistance to apoptosis induced by lipid peroxidation-causing agents such as H 2O 2, UVA, superoxide anion, and pro-oxidant xenobiotics, suggesting that signaling for apoptosis by these agents is transduced through HNE. Cells with the capacity to exclude HNE from the intracellular environment at a faster rate are relatively more resistant to apoptosis caused by H 2O 2, UVA, superoxide anion, and pro-oxidant xenobiotics as well as by HNE, suggesting that HNE may be a common denominator in mechanisms of apoptosis caused by oxidative stress. We have also shown that transfection of adherent cells with HNE-metabolizing GSTs leads to transformation of these cells due to depletion of HNE. These recent studies from our laboratories, which strongly suggest that HNE is a key signaling molecule and that GSTs, being determinants of its intracellular concentrations, can regulate stress-mediated signaling, are reviewed in this article.
ISSN:0891-5849
1873-4596
DOI:10.1016/j.freeradbiomed.2004.05.033