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.

Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine

“…Hence, cardiac mitochondrial dysfunction evoked by chronic iron overload might cause reduced ATP production in cardiomyocytes7. In addition, SERCA uses the free energy of ATP to transport Ca 2+ into the sarcoplasmic reticulum through a concentration gradient which leads to intracellular Ca 2+ homeostasis57. This may lead to a decrease in ATP levels in cardiac iron overload and cause reduced SERCA function and/or activity, which results in impaired Ca 2+ homeostasis as shown in our present study.…”

Pyridine nucleotide regulation of hepatic endoplasmic reticulum calcium uptake

“…Oxidation of protein sulfhydryl groups diminishes Ca 2+ ‐ATPase activity (Horakova et al. ). Several pyridine containing compounds were tested, with or without the antioxidants GSH and DTT (Fig.…”

“…SERCA2b) (Morris and Sulakhe 1997;Xu et al 1997;Li and Camacho 2004;Zima et al 2004;Gorlach et al 2006;Ozawa 2010;Gorlach et al 2015;Ushioda et al 2016). Oxidation of protein sulfhydryl groups diminishes Ca 2+ -ATPase activity (Horakova et al 2013). Several pyridine containing compounds were tested, with or without the antioxidants GSH and DTT (Fig.…”

New strategies focused on endoplasmic reticulum for treatment of human diseases

“…Flavonoids and other small molecules are able to elevate cytosolic (Ca 2+ ) at least partially via SERCA and thus may be a useful tool for preventing cancer development. On the other hand, some flavonoids significantly increased cell viability and protected against cardiomyocyte apoptosis via preservation of SERCA function, which can be a novel strategy against cardiovascular diseases associated with oxidative stress [3,4]. ER plays also a more important role in type 2 diabetes and its complications than believed previously.…”