Abstract
Eicosapentaenoic acid (EPA), an omega-3 fatty acid abundant in fish oil, protects endothelial cells (EC) from lipotoxicity and triggers EC NO release. The latter is related to an elevation of cytosolic Ca(2+). Although EPA has been shown to cause human EC cytosolic Ca(2+) elevation, the mechanism is unclear. Microfluorimetric imaging was used here to measure free cytosolic Ca(2+) concentration. EPA was shown to cause intracellular Ca(2+) release in mouse cerebral cortex endothelial bEND.3 cells; interestingly, the EPA-sensitive intracellular Ca(2+) pool(s) appeared to encompass and was larger than the Ca(2+) pool mobilized by sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase inhibition by cyclopiazonic acid. EPA also opened a Ca(2+) influx pathway pharmacologically distinct from store-operated Ca(2+) influx. Surprisingly, EPA-triggered Ca(2+) influx was Ni(2+)-insensitive; and EPA did not trigger Mn(2+) influx. Further, EPA-triggered Ca(2+) influx did not involve Na(+)-Ca(2+) exchangers. Thus, our results suggest EPA triggered unusual mechanisms of Ca(2+) release and Ca(2+) influx in EC.