Regulation by reversible S-glutathionylation: molecular targets implicated in inflammatory diseases.
S-glutathionylation is a reversible post-translational modification that continues to gain eminence as a redox regulatory mechanism of protein activity and associated cellular functions. Many diverse cellular proteins such as transcription factors, adhesion molecules, enzymes, and cytokines are reported to undergo glutathionylation, although the functional impact has been less well characterized. De-glutathionylation is catalyzed specifically and efficiently by glutaredoxin (GRx, aka thioltransferase), and facile reversibility is critical in determining the physiological relevance of glutathionylation as a means of protein regulation. Thus, studies with cohesive themes addressing both the glutathionylation of proteins and the corresponding impact of GRx are especially useful in advancing understanding. Reactive oxygen species (ROS) and redox regulation are well accepted as playing a role in inflammatory processes, such as leukostasis and the destruction of foreign particles by macrophages. We discuss in this review the current implications of GRx and/or glutathionylation in the inflammatory response and in diseases associated with chronic inflammation, namely diabetes, atherosclerosis, inflammatory lung disease, cancer, and Alzheimer's disease, and in viral infections.
Shelton
Melissa D
MD
Department of Pharmacology, School of Medicine, Case Western Reserve University, and Louis Stokes Cleveland Veterans Affairs Medical Research Center, Cleveland, Ohio 44106-4965, USA.
Mieyal
John J
JJ
D016207:Cytokines / Q000378:metabolism; D054477:Glutaredoxins / Q000096:biosynthesis / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000201:enzymology*; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology; D009000:Monocytes / Q000201:enzymology; D011499:Protein Processing, Post-Translational; D017382:Reactive Oxygen Species / Q000378:metabolism; D014777:Virus Diseases / Q000201:enzymology
D016207:Cytokines; D054477:Glutaredoxins; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; D005978:Glutathione