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


BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Myocardial Biology Unit, Whitaker Cardiovascular Institute, Boston University School of Medicine, Massachusetts, USA.
David
D
Pimentel
Dagmar Johanna
DJ
Haeussler
Reiko
R
Matsui
Joseph Robert
JR
Burgoyne
Richard Alan
RA
Cohen
Markus Michael
MM
Bachschmid
D000818:Animals; D002319:Cardiovascular System / Q000378:metabolism*; D002477:Cells / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D011506:Proteins / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism
D011506:Proteins; D013438:Sulfhydryl Compounds; D005978:Glutathione