Regulation of cellular thiol redox status by nitric oxide.
Nitric oxide (NO) is an important biological molecule that participates in a wide range of responses, including vasodilation, platelet regulation, neurotransmission, and cytoxicity. NO's most widely known and best understood mechanism of action is through its interaction with the heme group in proteins such as soluble guanylate cyclase. In addition to heme iron, NO has also been shown to react with other functional groups in proteins. However, it is becoming clear that many reactions previously attributed to NO are now known to be mediated through NO-derived species (NOx) and not directly through NO itself (as discussed below). The thiol group of cysteine residues represents one potential target of NOx and may be of particular biological relevance since cysteines are important for maintaining the native conformation of proteins, are critical to the activity of many enzymes, and are the most reactive amino acid residues at physiological pH. In fact, modification of protein thiols by NOx alters the function and activity of various proteins including enzymes, signaling proteins, ion channels, receptors, transcription factors, and antioxidants. These alterations in protein function, through modification of thiols, may be critical for initiating signaling events or may be detrimental to the cell by disrupting essential protein function. This article aims to review the interactions of NOx with protein and nonprotein thiols, including mechanisms of thiol modification, reversibility of NOx-mediated protein thiol modification, and cellular defense mechanisms involved in regulating NOx-mediated modification of protein thiols.
Padgett
C M
CM
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710, USA.
Whorton
A R
AR
D000818:Animals; D003545:Cysteine / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism; D004789:Enzyme Activation; D005978:Glutathione / Q000378:metabolism; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D004220:Disulfides; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide; D005978:Glutathione; D003545:Cysteine