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. 2008 Oct 11;65(22):3640–3652. doi: 10.1007/s00018-008-8383-9

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

S H Wang 1,6, Y L Shih 2,3, W C Ko 4, Y H Wei 5, C M Shih 1,6,
PMCID: PMC11131605  PMID: 18850067

Abstract.

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.

Electronic supplementary material

The online version of this article (doi:10.1007/s00018-008-8383-9) contains supplementary material, which is available to authorized users.

Keywords. Autophagy, apoptosis, cadmium, calcium, calcineurin, ERK, mitochondria

Electronic Supplementary material

(PDF 170 kb) (169.6KB, pdf)

Footnotes

Received 05 July 2008; received after revision 25 August 2008; accepted 17 September 2008

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(PDF 170 kb) (169.6KB, pdf)

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