1. Early release and subsequent caspase-mediated degradation of cytochrome c in apoptotic cerebellar granule cells.
- Author
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Bobba A, Atlante A, Giannattasio S, Sgaramella G, Calissano P, and Marra E
- Subjects
- Adenylate Kinase metabolism, Amino Acid Chloromethyl Ketones pharmacology, Animals, Apoptosis drug effects, Cells, Cultured, Cysteine Proteinase Inhibitors pharmacology, Cytosol metabolism, Glutamate Dehydrogenase metabolism, Immunoblotting, Mitochondria metabolism, Oxygen Consumption, Polarography, Rats, Time Factors, Apoptosis physiology, Caspases metabolism, Cerebellum metabolism, Cytochrome c Group metabolism
- Abstract
Cytochrome c (cyt c) release was investigated in cerebellar granule cells used as an in vitro neuronal model of apoptosis. We have found that cyt c is released into the cytoplasm as an intact, functionally active protein, that this event occurs early, in the commitment phase of the apoptotic process, and that after accumulation, this protein is progressively degraded. Degradation, but not release, is fully blocked by benzyloxycarbonyl-Val-Ala-Asp-fluoromethylchetone (z-VAD-fmk). On the basis of previous findings obtained in the same neuronal population undergoing excitotoxic death, it is hypothesized that release of cyt c may be part of a cellular attempt to maintain production of ATP via cytochrome oxidase, which is reduced by cytosolic NADH in a cytochrome b5-soluble cyt c-mediated fashion.
- Published
- 1999
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