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

Research output: Contribution to journalArticlepeer-review

201 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)3640-3652
Number of pages13
JournalCellular and Molecular Life Sciences
Issue number22
Publication statusPublished - Nov 2008


  • Apoptosis
  • Autophagy
  • Cadmium
  • Calcineurin
  • Calcium
  • ERK
  • Mitochondria

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology


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