title: Impairment of calcium ATPases by high glucose and potential pharmacological protection.
abstract: The review deals with impairment of Ca(2+)-ATPases by high glucose or its derivatives in vitro, as well as in human diabetes and experimental animal models. Acute increases in glucose level strongly correlate with oxidative stress. Dysfunction of Ca(2+)-ATPases in diabetic and in some cases even in nondiabetic conditions may result in nitration of and in irreversible modification of cysteine-674. Nonenyzmatic protein glycation might lead to alteration of Ca(2+)-ATPase structure and function contributing to Ca(2+) imbalance and thus may be involved in development of chronic complications of diabetes. The susceptibility to glycation is probably due to the relatively high percentage of lysine and arginine residues at the ATP binding and phosphorylation domains. Reversible glycation may develop into irreversible modifications (advanced glycation end products, AGEs). Sites of SERCA AGEs are depicted in this review. Finally, several mechanisms of prevention of Ca(2+)-pump glycation, and their advantages and disadvantages are discussed.
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, SAS, Bratislava, Slovakia. exfahorl@savba.sk
authors.forename: L
authors.initials: L
authors.lastname: Horáková
authors.forename: M K
authors.initials: MK
authors.lastname: Strosova
authors.forename: C M
authors.initials: CM
authors.lastname: Spickett
authors.forename: D
authors.initials: D
authors.lastname: Blaskovic
mesh_terms: D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000187:drug effects / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005947:Glucose / Q000008:administration & dosage*; D017127:Glycation End Products, Advanced / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011108:Polymers / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D011108:Polymers; C024617:polyol; C002744:3-nitrotyrosine; D014443:Tyrosine; D000252:Calcium-Transporting ATPases; D005947:Glucose; D008239:Lysine; D002118:Calcium