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

4-Hydroxy-trans-2-nonenal (HNE) was initially considered to be merely a toxic end product of lipid peroxidation that contributed to oxidative stress-related pathogenesis. However, in recent years its physiological role as an important "signaling molecule" has been established. HNE can modulate various signaling pathways in a concentration-dependent manner. Glutathione S-transferases (GSTs) are major determinants of the intracellular concentration of HNE, because these enzymes account for the metabolism of most cellular HNE through its conjugation to glutathione. Evidence is emerging that GSTs are involved in the regulation of the HNE-mediated signaling processes. Against the backdrop of our current understanding on the formation, metabolism, and role of HNE in signaling processes, the physiological role of GSTs in regulation of HNE-mediated signaling processes is critically evaluated in this chapter. Available evidence strongly suggests that besides their well-established pharmacological role of detoxifying xenobiotics, GSTs also play an important physiological role in the regulation of cellular signaling processes.