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Regulation of cell physiology and pathology by protein S-glutathionylation: lessons learned from the cardiovascular system.

Abstract：

SIGNIFICANCE:Reactive oxygen and nitrogen species contributing to homeostatic regulation and the pathogenesis of various cardiovascular diseases, including atherosclerosis, hypertension, endothelial dysfunction, and cardiac hypertrophy, is well established. The ability of oxidant species to mediate such effects is in part dependent on their ability to induce specific modifications on particular amino acids, which alter protein function leading to changes in cell signaling and function. The thiol containing amino acids, methionine and cysteine, are the only oxidized amino acids that undergo reduction by cellular enzymes and are, therefore, prime candidates in regulating physiological signaling. Various reports illustrate the significance of reversible oxidative modifications on cysteine thiols and their importance in modulating cardiovascular function and physiology. RECENT ADVANCES:The use of mass spectrometry, novel labeling techniques, and live cell imaging illustrate the emerging importance of reversible thiol modifications in cellular redox signaling and have advanced our analytical abilities. CRITICAL ISSUES:Distinguishing redox signaling from oxidative stress remains unclear. S-nitrosylation as a precursor of S-glutathionylation is controversial and needs further clarification. Subcellular distribution of glutathione (GSH) may play an important role in local regulation, and targeted tools need to be developed. Furthermore, cellular redundancies of thiol metabolism complicate analysis and interpretation. FUTURE DIRECTIONS:The development of novel pharmacological analogs that specifically target subcellular compartments of GSH to promote or prevent local protein S-glutathionylation as well as the establishment of conditional gene ablation and transgenic animal models are needed.

journal_name

Antioxid Redox Signal

journal_title

Antioxidants & redox signaling

authors

Pimentel D,Haeussler DJ,Matsui R,Burgoyne JR,Cohen RA,Bachschmid MM

doi

10.1089/ars.2011.4336

subject

Has Abstract

pub_date

2012-03-15 00:00:00

pages

524-42

issue

eissn

1523-0864

issn

1557-7716

journal_volume

pub_type

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Regulation of cell physiology and pathology by protein S-glutathionylation: lessons learned from the cardiovascular system.