Curcumin induces intracellular calcium depletion via a mitochondrial uniporter pathway in PC12 cells

Abstract

Curcumin, a natural, biologically active compound extracted from rhizomes of Curcuma species, has been shown to possess the potent properties for regulation of cell proliferation. Although intracellular calcium status is very closely linked with various cellular functions, the action mechanism of curcumin on intracellular calcium signalling remains poorly understood. This study was investigated the effect of curcumin on intracellular calcium concentration ([Ca2+]i) using a calcium indicator dye Fura-2 in PC12 cells. Curcumin induced a marked depletion of [Ca2+]i in PC12 cells bathed with both Ca2+-containing and Ca2+-free bath solution. To clarify the effects of curcumin on the levels of plasma membrane, extracellular Na+- free solution and vanadate were applicated on the cells but these did not affect the curcumin effect. Both thapsigargin, a specific inhibitor of sarco/endoplasmic reticulum Ca2+-ATPase, and carbonyl cyanide 3-chlorophenylhydrazone, a mitochondrial uncoupler, also did not change the effect of curcumin on [Ca2+]i. However, ruthenium red, an inhibitor of mitochondrial uniporter, blocked the curcumin-induced [Ca2+]i depletion in dose-dependent manner with ED50 of 2.7 ± 0.14 μM. Present study demonstrates that curcumin induces the intracellular calcium uptake into mitochondria via a uniporter pathway and may involve in the modulation of cellular function and proliferation.