Protein Thiol Redox Signaling in Monocytes and Macrophages.
Monocyte and macrophage dysfunction plays a critical role in a wide range of inflammatory disease processes, including obesity, impaired wound healing diabetic complications, and atherosclerosis. Emerging evidence suggests that the earliest events in monocyte or macrophage dysregulation include elevated reactive oxygen species production, thiol modifications, and disruption of redox-sensitive signaling pathways. This review focuses on the current state of research in thiol redox signaling in monocytes and macrophages, including (i) the molecular mechanisms by which reversible protein-S-glutathionylation occurs, (ii) the identification of bona fide S-glutathionylated proteins that occur under physiological conditions, and (iii) how disruptions of thiol redox signaling affect monocyte and macrophage functions and contribute to atherosclerosis. Recent Advances: Recent advances in redox biochemistry and biology as well as redox proteomic techniques have led to the identification of many new thiol redox-regulated proteins and pathways. In addition, major advances have been made in expanding the list of S-glutathionylated proteins and assessing the role that protein-S-glutathionylation and S-glutathionylation-regulating enzymes play in monocyte and macrophage functions, including monocyte transmigration, macrophage polarization, foam cell formation, and macrophage cell death.



Protein-S-glutathionylation/deglutathionylation in monocytes and macrophages has emerged as a new and important signaling paradigm, which provides a molecular basis for the well-established relationship between metabolic disorders, oxidative stress, and cardiovascular diseases.



The identification of specific S-glutathionylated proteins as well as the mechanisms that control this post-translational protein modification in monocytes and macrophages will facilitate the development of new preventive and therapeutic strategies to combat atherosclerosis and other metabolic diseases. Antioxid. Redox Signal. 25, 816-835.
1 Department of Pharmacology, University of Texas Health Science Center at San Antonio , San Antonio, Texas.
John D
JD
Short
2 Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio , San Antonio, Texas.
Kevin
K
Downs
3 Department of Radiology, University of Texas Health Science Center at San Antonio , San Antonio, Texas.
Sina
S
Tavakoli
4 Department of Clinical Laboratory Sciences, University of Texas Health Science Center at San Antonio , San Antonio, Texas.|5 Department of Biochemistry, University of Texas Health Science Center at San Antonio , San Antonio, Texas.
Reto
R
Asmis
D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D011506:Proteins; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D005978:Glutathione
S-glutathionylation; atherosclerosis; macrophage; redox signaling; thiols