Resveratrol inhibits plasma membrane Ca2+-ATPase inducing an increase in cytoplasmic calcium

Joshua Allen Peterson; Richard Vernon Oblad; Jeffrey Chad Mecham; Jason Donald Kenealey

doi:10.1016/j.bbrep.2016.06.019

Resveratrol inhibits plasma membrane Ca²⁺-ATPase inducing an increase in cytoplasmic calcium

Biochem Biophys Rep. 2016 Jun 30:7:253-258. doi: 10.1016/j.bbrep.2016.06.019. eCollection 2016 Sep.

Authors

Joshua Allen Peterson¹, Richard Vernon Oblad¹, Jeffrey Chad Mecham¹, Jason Donald Kenealey¹

Affiliation

¹ Department of Nutrition, Dietetics and Food Science, Brigham Young University, ESC S-127, Provo, UT, United States.

Abstract

Plasma membrane Ca²⁺-ATPase (PMCA) plays a vital role in maintaining cytosolic calcium concentration ([Ca²⁺] _i ). Given that many diseases have modified PMCA expression and activity, PMCA is an important potential target for therapeutic treatment. This study demonstrates that the non-toxic, naturally-occurring polyphenol resveratrol (RES) induces increases in [Ca²⁺] _i via PMCA inhibition in primary dermal fibroblasts and MDA-MB-231 breast cancer cells. Our results also illustrate that RES and the fluorescent intracellular calcium indicator Fura-2, are compatible for simultaneous use, in contrast to previous studies, which indicated that RES modulates the Fura-2 fluorescence independent of calcium concentration. Because RES has been identified as a PMCA inhibitor, further studies may be conducted to develop more specific PMCA inhibitors from RES derivatives for potential therapeutic use.

Keywords: BAPTA, BAPTA-Acetoxymethyl ester; Calcium signaling; DMEM, Dulbecco's modified Eagle medium; DMSO, dimethyl sulfoxide; EGCG, epigallocatechin gallate; ER, endoplasmic reticulum; FBS, fetal bovine serum; Fura-2; Fura-2, Fura-2-Acetoxymethyl ester; HBSS, Ca2+- and Mg2+-free Hank's Balanced Salt Solution; PBS, phosphate-buffered saline; PMCA, plasma membrane Ca2+-ATPase; Plasma membrane Ca2+-ATPase; RES, resveratrol; ROI, region of interest; Resveratrol; SERCA, sarcoendoplasmic reticular Ca2+-ATPase; TG, thapsigargin; [Ca2+]i, cytosolic calcium concentration.