title: Inhibitors of advanced glycation and endoplasmic reticulum stress.
abstract: Advanced glycation is one of the major pathophysiological posttranslational modifications. Under hyperglycemic conditions or oxidative stress, proteins and DNA are nonenzymatically modified by oxidative glycation and converted to advanced glycation endproducts (AGEs), which induce the loss of protein functions or apoptosis. This conversion to AGEs leads to the disease progression of hyperglycemia- or oxidative stress-related diseases, such as diabetic mellitus and its complications, neurodegenerative disease, atherosclerosis, and kidney disease. Further, recent evidence indicates that advanced glycation is initiated not only by oxidative stress but also by hypoxia, suggesting its pathogenesis across a wide range of diseases associated with aberrant oxygen tension as well as glucose metabolism. In addition to their role in triggering advanced glycation, these disturbances are also well known as initiators of endoplasmic reticulum (ER) stress, and of the consequent unfolded protein response (UPR). These findings strongly indicate the presence of cross talk between advanced glycation and ER stress in disease progression. In this chapter, I focus on the link between advanced glycation and ER stress, and the potential use of inhibitors of AGE formation as modulators of ER stress.
authors.affiliation: Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Inagi
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D018384:Oxidative Stress / Q000187:drug effects; D056811:Unfolded Protein Response / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D000975:Antioxidants; D017127:Glycation End Products, Advanced