Cadmium, a toxic environmental contaminant, exerts adverse effects on different cellular pathways such as cell proliferation, DNA damage and apoptosis. In particular, the modulation of Ca2+ homeostasis seems to have an important role during Cd2+ injury, but the precise assessment of Ca2+ signalling still remains poorly understood.We used aequorin-based probes specifically directed to intracellular organelles to study Ca2+ changes during cadmium injury. We observed that cadmium decreased agonist-evoked endoplasmic reticulum (ER) Ca2+ signals and caused a 40% inhibition of sarcoplasmic–ER calcium ATPases activity. Moreover, time course experiments correlate morphological alterations, processing of xbp-1 mRNA and caspase-12 activation during cadmium administration. Finally, the time response of ER to cadmium injury was compared with that of mitochondria. In conclusion, we highlighted a novel pathway of cadmium-induced cell death triggered by ER stress and involving caspase-12. Mitochondria and ER pathways seemed to share common time courses and a parallel activation of caspase-12 and caspase-9 seemed likely to be involved in acute cadmium toxicity.v
Autori interni: | |
Autori: | BIAGIOLI M; PIFFERI S; RAGGHIANTI M; BUCCI S; RIZZUTO R; PINTON P |
Titolo: | Endoplasmic reticulum stress and alteration in calcium homeostasis are involved in cadmium-induced apoptosis |
Anno del prodotto: | 2008 |
Digital Object Identifier (DOI): | 10.1016/j.ceca.2007.05.003 |
Appare nelle tipologie: | 1.1 Articolo in rivista |