Inhibition of the intracellular Ca(2+) transporter SERCA (Sarco-Endoplasmic Reticulum Ca(2+)-ATPase) by the natural polyphenol epigallocatechin-3-gallate.

Inhibition of the intracellular Ca(2+) transporter SERCA (Sarco-Endoplasmic Reticulum Ca(2+)-ATPase) by the natural polyphenol epigallocatechin-3-gallate.

J Bioenerg Biomembr. 2012 Aug 1;

Authors: Soler F, Asensio MC, Fern�ndez-Belda F

Abstract
The use of a microsomal preparation from skeletal muscle revealed that both Ca(2+) transport and Ca(2+)-dependent ATP hydrolysis linked to Sarco-Endoplasmic Reticulum Ca(2+)-ATPase are inhibited by epigallocatechin-3-gallate (EGCG). A half-maximal effect was achieved at approx. 12�?M. The presence of the galloyl group was essential for the inhibitory effect of the catechin. The relative inhibition of the Ca(2+)-ATPase activity decreased when the Ca(2+) concentration was raised but not when the ATP concentration was elevated. Data on the catalytic cycle indicated inhibition of maximal Ca(2+) binding and a decrease in Ca(2+) binding affinity when measured in the absence of ATP. Moreover, the addition of ATP to samples in the presence of EGCG and Ca(2+) led to an early increase in phosphoenzyme followed by a time-dependent decay that was faster when the drug concentration was raised. However, phosphorylation following the addition of ATP plus Ca(2+) led to a slow rate of phosphoenzyme accumulation that was also dependent on EGCG concentration. The results are consistent with retention of the transporter conformation in the Ca(2+)-free state, thus impeding Ca(2+) binding and therefore the subsequent steps when ATP is added to trigger the Ca(2+) transport process. Furthermore, phosphorylation by inorganic phosphate in the absence of Ca(2+) was partially inhibited by EGCG, suggesting alteration of the native Ca(2+)-free conformation at the catalytic site.

PMID: 22851007 [PubMed - as supplied by publisher]

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