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 Ca(2+) in the activation of ERK1/2 and whether Ca(2+) 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 Ca(2+) mobilization and the extracellular Ca(2+) 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 Ca(2+) chelator, and partially inhibited by EGTA, an extracellular Ca(2+) chelator, or verapamil, an L-type Ca(2+) channel blocker. These findings suggest that Ca(2+) may play an important role in angiotensin II-induced ERK1/2 activation in VSMCs, and Ca(2+)-dependent pathway may be involved in the inhibitory effect by crocetin of angiotensin II-induced ERK1/2 activation.
Zhou
Cheng-Hua
CH
Department of Pharmacology, China Pharmaceutical University, Tongjia Xiang 24, Nanjing 210009, PR China.
Qian
Zhi-Yu
ZY
Xiang
Min
M
He
Shu-Ying
SY
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002338:Carotenoids / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology; D014801:Vitamin A / Q000031:analogs & derivatives
D002121:Calcium Channel Blockers; D002614:Chelating Agents; C487773:trans-sodium crocetinate; D014801:Vitamin A; D000804:Angiotensin II; D002338:Carotenoids; D004533:Egtazic Acid; D014700:Verapamil; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D002118:Calcium