Involvement of Ca2+ in the inhibition by crocetin of angiotensin II-induced ERK1/2 activation in vascular smooth muscle cells

Crocetin, a carotenoid compound, was isolated from Gardenia jasminoids Ellis. Our recent study shows that crocetin inhibits angiotensin II-induced extracellular signal-regulated kinases 1/2 (ERK1/2) activation and subsequent proliferation in vascular smooth muscle cells (VSMCs). To further explore the mechanism involved, in the present study, we investigated the effect of Ca2+ in the activation of ERK1/2 and whether Ca2+ is involved in the suppression by crocetin of angiotensin II-induced ERK1/2 activation. Our findings showed that crocetin pretreatment partially attenuated both the intracellular Ca2+ mobilization and the extracellular Ca2+ influx induced by angiotensin II. Moreover, angiotensin II-induced ERK1/2 activation was completely abolished by acetoxymethyl ester of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM), an intracellular Ca2+ chelator, and partially inhibited by EGTA, an extracellular Ca2+ Chelator, or verapamil, an L-type Ca2+ channel blocker. These findings suggest that Ca2+ may play an important role in angiotensin II-induced ERK1/2 activation in VSMCs, and Ca2+-dependent pathway may be involved in the inhibitory effect by crocetin of angiotensin II-induced ERK1/2 activation. (c) 2006 Elsevier B.V. All rights reserved.