title: Cellular mechanisms and consequences of glycation in atherosclerosis and obesity.
abstract: Post-translational modification of proteins imparts diversity to protein functions. The process of glycation represents a complex set of pathways that mediates advanced glycation endproduct (AGE) formation, detoxification, intracellular disposition, extracellular release, and induction of signal transduction. These processes modulate the response to hyperglycemia, obesity, aging, inflammation, and renal failure, in which AGE formation and accumulation is facilitated. It has been shown that endogenous anti-AGE protective mechanisms are thwarted in chronic disease, thereby amplifying accumulation and detrimental cellular actions of these species. Atop these considerations, receptor for advanced glycation endproducts (RAGE)-mediated pathways downregulate expression and activity of the key anti-AGE detoxification enzyme, glyoxalase-1 (GLO1), thereby setting in motion an interminable feed-forward loop in which AGE-mediated cellular perturbation is not readily extinguished. In this review, we consider recent work in the field highlighting roles for glycation in obesity and atherosclerosis and discuss emerging strategies to block the adverse consequences of AGEs. This article is part of a Special Issue entitled: The role of post-translational protein modifications on heart and vascular metabolism edited by Jason R.B. Dyck & Jan F.C. Glatz.
authors.affiliation: Diabetes Research Program, Division of Endocrinology, Department of Medicine, NYU Langone Medical Center, New York, NY 10016, United States.
authors.forename: Raquel
authors.initials: R
authors.lastname: López-Díez
authors.affiliation: Department of Chemistry, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, United States.
authors.forename: Alexander
authors.initials: A
authors.lastname: Shekhtman
authors.affiliation: Diabetes Research Program, Division of Endocrinology, Department of Medicine, NYU Langone Medical Center, New York, NY 10016, United States.
authors.forename: Ravichandran
authors.initials: R
authors.lastname: Ramasamy
authors.affiliation: Diabetes Research Program, Division of Endocrinology, Department of Medicine, NYU Langone Medical Center, New York, NY 10016, United States. Electronic address: annmarie.schmidt@nyumc.org.
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D011499:Protein Processing, Post-Translational; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*
chemical_list: C000593871:AGER protein, human; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; C000597196:GLO1 protein, human; D007791:Lactoylglutathione Lyase
keywords: Atherosclerosis; Diabetes; Glycation; Obesity; Receptor for advanced glycation end products; Theraepeutics