title: Crosstalk between advanced glycation and endoplasmic reticulum stress: emerging therapeutic targeting for metabolic diseases.
abstract: BACKGROUND
  Advanced glycation, the major posttranslational modification of proteins, DNA, and lipids, is accelerated under conditions of increased oxidative stress, hyperglycemia, and hypoxia contributing to a variety of metabolic diseases such as diabetes mellitus, obesity, inflammation, polycystic ovarian syndrome, ischemic cardiovascular disease, and neurodegenerative disorders. The potential role of advanced glycation in endoplasmic reticulum (ER) homeostasis is largely unknown.
  
  
  METHODS
  Basic and clinical peer-reviewed articles on advanced glycation and ER stress related to metabolic regulation were searched in PubMed from 2000-2011. The resulting articles as well as relevant cited references were reviewed.
  
  
  RESULTS
  Recent evidence indicates that hyperglycemia, hypoxia, and oxidative stress, apart of triggering advanced glycation, can also adversely affect ER function, leading to pathogenic ER stress, followed by the unfolded protein response. The concomitant presence of advanced glycation in the same conditions with ER stress suggests their crosstalk in the progression of diseases associated with hypoxic and oxidative stress.
  
  
  CONCLUSIONS
  Current data support the direct or indirect induction of ER stress response by advanced glycation end products or advanced glycation end product precursors in the pathogenesis of metabolic diseases. Inhibitors of advanced glycation acting as potent ER stress modulators with beneficial effects in restoring ER homeostasis and adjusting physiological unfolded protein response level present an emerging therapeutic approach with significant applications, especially in the context of metabolic dysfunction.
authors.affiliation: Department of Biological Chemistry, Medical School, University of Athens, 75, M. Asias Street, 11527 Athens, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Piperi
authors.forename: Christos
authors.initials: C
authors.lastname: Adamopoulos
authors.forename: Georgia
authors.initials: G
authors.lastname: Dalagiorgou
authors.forename: Evanthia
authors.initials: E
authors.lastname: Diamanti-Kandarakis
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Papavassiliou
mesh_terms: D004704:Endocrinology / Q000379:methods / Q000639:trends; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D017127:Glycation End Products, Advanced / Q000378:metabolism* / Q000502:physiology*; D006031:Glycosylation; D006801:Humans; D008659:Metabolic Diseases / Q000628:therapy*; D008954:Models, Biological; D020239:Receptor Cross-Talk / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D035703:Therapies, Investigational / Q000379:methods / Q000639:trends*
chemical_list: D017127:Glycation End Products, Advanced