NDLI: Inhibition of the intracellular Ca$^{2+}$ transporter SERCA (Sarco-Endoplasmic Reticulum Ca$^{2+}$-ATPase) by the natural polyphenol epigallocatechin-3-gallate

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

Content Provider	Springer Nature Link
Author	Soler, Fernando Asensio, M. Carmen Fernández Belda, Francisco
Copyright Year	2012
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 μM. 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.
Starting Page	597
Ending Page	605
Page Count	9
File Format	PDF
ISSN	0145479X
Journal	Journal of Bioenergetics and Biomembranes
Volume Number	44
Issue Number	5
e-ISSN	15736881
Language	English
Publisher	Springer US
Publisher Date	2012-08-01
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Ca$^{2+}$-ATPase Epigallocatechin-3-gallate Inhibition mechanism Hydrolytic and transport cycle Phosphoenzyme Sarcoplasmic reticulum Organic Chemistry Animal Anatomy / Morphology / Histology Biochemistry Bioorganic Chemistry Animal Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Physiology

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