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

Endoplasmic reticulum stress and alteration in calcium homeostasis are involved in cadmium-induced apoptosis

RAGGHIANTI, MATILDE;
2008

Abstract

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
Biagioli, M; Pifferi, S; Ragghianti, Matilde; Bucci, S; Rizzuto, R; Pinton, P.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/118496
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