Nitric Oxide and Mechanisms of Redox Signaling

Abstract

Regulation of signal transduction and gene expression is a multifaceted process involving ligands, receptors, and second messengers that trigger cascades of protein kinases and phosphatases and propagate the signal to the nucleus to alter gene expression. Reduction-oxidation (redox)-based regulatory pathways provide additional means of gating signal transduction, and redox-based regulation of gene expression emerges as a fundamental regulatory mechanism in living cells. The cellular redox state is reflected by the degree of oxidation (or reduction) of various redox-active molecules at a specific cellular location at any given time point. The ratio of oxidized/reduced redox species determines the redox potential, which may vary dramatically in time and in different compartments of a cell and consequently alter in a temporally and spatially dynamic process the activity of signaling enzymes that carry redox-active functional groups. Generation and action of free radicals such as nitric oxide, superoxide, and H(2)O(2) that paradigmatically highlight the impact of redox regulation on cellular signal transduction and gene expression are discussed with a special focus on the renal glomerular response to injury.