Endoplasmic reticulum stress and alteration in calcium homeostasis are involved in cadmium-induced apoptosis
| Autor: | Rosario Rizzuto, Simone Pifferi, Matilde Ragghianti, Stefania Bucci, Marta Biagioli, Paolo Pinton |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
inorganic chemicals
X-Box Binding Protein 1 Programmed cell death Protein Folding Physiology caspase ENDOPLASMIC-RETICULUM Ca2+ homeostasis chemistry.chemical_element Apoptosis Regulatory Factor X Transcription Factors Calcium Biology Bradykinin Endoplasmic Reticulum Transfection Mice Aequorin Cadmium Ca2+-ATPase Animals Homeostasis Calcium Signaling Molecular Biology Caspase 12 Calcium signaling Calcium metabolism Endoplasmic reticulum Cytochromes c Cell Biology Cell biology Mitochondria DNA-Binding Proteins Enzyme Activation chemistry Unfolded protein response NIH 3T3 Cells Transcription Factors |
| Popis: | 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 Ca(2+) homeostasis seems to have an important role during Cd(2+) injury, but the precise assessment of Ca(2+) signalling still remains poorly understood. We used aequorin-based probes specifically directed to intracellular organelles to study Ca(2+) changes during cadmium injury. We observed that cadmium decreased agonist-evoked endoplasmic reticulum (ER) Ca(2+) 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. |
| Databáze: | OpenAIRE |
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