Impairment of calcium ATPases by high glucose and potential pharmacological protection

Abstract

The review deals with impairment of Ca²⁺-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 Ca²⁺-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 Ca²⁺-ATPase structure and function contributing to Ca²⁺ 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 Ca²⁺-pump glycation, and their advantages and disadvantages are discussed.

Keywords::

• polyol
• pathway
• glycation
• cysteine-674
• nitrotyrosine
• diabetes

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.

This work was supported by COST action CM 1001, by VEGA 2/0038/11, and by The Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic for the Structural Funds of EU, OP R&D of ERDF by realization of the Project Evaluation of natural substances and their selection for prevention and treatment of lifestyle diseases (ITMS 26240220040).