Cadmium-induced autophagy and apoptosis are mediated by a calcium signaling pathway

S. H. Wang, Y. L. Shih, W. C. Ko, Y. H. Wei, C. M. Shih

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178 引文 斯高帕斯(Scopus)

摘要

The cytotoxicity of cadmium (Cd) induced autophagy and apoptosis in MES-13 cells was determined by flow cytometry. Autophagy was also assessed by formation of autophagosomes and processing of LC3. Pharmacological inhibition of autophagy resulted in increased of cell viability, suggesting autophagy plays a role in cell death in Cd-treated mesangial cells. Cd also induced a rapid elevation in cytosolic calcium ([Ca2+]i ), and modulation of [Ca2+]i via treatment with IP 3R inhibitor or knockdown of calcineurin resulted in a change in the proportion of cell death, suggesting that the release of calcium from the ER plays a crucial role in Cd-induced cell death. Inhibition of Cd-induced ERK activation by PD 98059 suppressed Cd-induced autophagy, and BAPTA-AM eliminated activation of ERK. BAPTA-AM also inhibited Cd-induced mitochondrial depolarization and activation of caspases. These findings demonstrated that Cd induces both autophagy and apoptosis through elevation of [Ca2+]i, followed by Ca2+-ERK and Ca2+-mitochondria-caspase signaling pathways.

原文英語
頁(從 - 到)3640-3652
頁數13
期刊Cellular and Molecular Life Sciences
65
發行號22
DOIs
出版狀態已發佈 - 十一月 2008

ASJC Scopus subject areas

  • 分子醫學
  • 分子生物學
  • 藥理
  • 細胞與分子神經科學
  • 細胞生物學

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