title: S-glutathionylation in monocyte and macrophage (dys)function.
abstract: Atherosclerosis is a chronic inflammatory disease involving the accumulation of monocytes and macrophages in the vascular wall. Monocytes and macrophages play a central role in the initiation and progression of atherosclerotic lesion development. Oxidative stress, which occurs when reactive oxygen species (ROS) overwhelm cellular antioxidant systems, contributes to the pathophysiology of many chronic inflammatory diseases, including atherosclerosis. Major targets of ROS are reactive thiols on cysteine residues in proteins, which when oxidized can alter cellular processes, including signaling pathways, metabolic pathways, transcription, and translation. Protein-S-glutathionylation is the process of mixed disulfide formation between glutathione (GSH) and protein thiols. Until recently, protein-S-glutathionylation was associated with increased cellular oxidative stress, but S-glutathionylation of key protein targets has now emerged as a physiologically important redox signaling mechanism, which when dysregulated contributes to a variety of disease processes. In this review, we will explore the role of thiol oxidative stress and protein-S-glutathionylation in monocyte and macrophage dysfunction as a mechanistic link between oxidative stress associated with metabolic disorders and chronic inflammatory diseases, including atherosclerosis.
authors.affiliation: Department of Biochemistry, University of Texas Health Science Center San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. ullevigs@uthscsa.edu
authors.forename: Sarah
authors.initials: S
authors.lastname: Ullevig
authors.forename: Hong Seok
authors.initials: HS
authors.lastname: Kim
authors.forename: Reto
authors.initials: R
authors.lastname: Asmis
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000276:immunology*; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000276:immunology*; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D011506:Proteins; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D019255:NADPH Oxidases; D005978:Glutathione