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Titolo: CERAMIDE FORMATION LEADS TO CASPASE-3 ACTIVATION DURING HYPOXIC PC12 CELL-DEATH - INHIBITORY EFFECTS OF BCL-2 ON CERAMIDE FORMATION AND CASPASE-3 ACTIVATION
Autore: YOSHIMURA S; BANNO Y; NAKASHIMA S; TAKENAKA K; SAKAI H; NISHIMURA Y; SAKAI N; SHIMIZU S; EGUCHI Y; TSUJIMOTO Y; NOZAWA Y;
- Indirizzi:
- GIFU UNIV,SCH MED,DEPT NEUROSURG,TSUKASAMACHI 40 GIFU 5008705 JAPAN GIFU UNIV,SCH MED,DEPT BIOCHEM GIFU 5008705 JAPAN OSAKA UNIV,SCH MED,BIOMED RES CTR,DEPT MED GENET SUITA OSAKA 565 JAPAN
- Titolo Testata:
- The Journal of biological chemistry
fascicolo: 12,
volume: 273,
anno: 1998,
pagine: 6921 - 6927
- SICI:
- 0021-9258(1998)273:12<6921:CFLTCA>2.0.ZU;2-Q
- Fonte:
- ISI
- Lingua:
- ENG
- Soggetto:
- HUMAN FOLLICULAR LYMPHOMA; NECROSIS-FACTOR-ALPHA; INDUCED APOPTOSIS; ICE/CED-3 PROTEASE; CHROMOSOMAL BREAKPOINT; SPHINGOMYELIN TURNOVER; MAMMALIAN HOMOLOG; FREE SYSTEM; GENE CED-3; EXPRESSION;
- Tipo documento:
- Article
- Natura:
- Periodico
- Settore Disciplinare:
- Science Citation Index Expanded
- Citazioni:
- 58
- Recensione:
- Indirizzi per estratti:
-
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- Citazione:
- S. Yoshimura et al., "CERAMIDE FORMATION LEADS TO CASPASE-3 ACTIVATION DURING HYPOXIC PC12 CELL-DEATH - INHIBITORY EFFECTS OF BCL-2 ON CERAMIDE FORMATION AND CASPASE-3 ACTIVATION", The Journal of biological chemistry, 273(12), 1998, pp. 6921-6927
Abstract
PC12 cells undergo apoptosis as well as necrosis following exposure to hypoxia. Following a 6-h hypoxic treatment, a time-dependent increase in intracellular ceramide level was observed with a concurrent decrease in sphingomyelin. It was also shown that the hypoxia-induced ceramide accumulation resulted from activation of neutral magnesium-dependent sphingomyelinase. Comparative kinetic analyses of the neutral sphingomyelinase in the cells under normoxia and hypoxia showed that hypoxia increased V-max but did not affect K-m of the enzyme. In PC12 cells overexpressing Bcl-2 which show strong resistance to hypoxia, sphingomyelin hydrolysis was decreased and activation of neutral sphingomyelinase was reduced. Addition of exogenous C-2-ceramide induced cell deathand activated caspase-3 as markedly as the hypoxia treatment. On the other hand, in PC12 cells overexpressing Bcl-2, significant decreases in cell death and inhibition of caspase-3 activation were observed after exogenous addition of C, ceramide. The inhibitors of caspase-3 prevented cell death by either hypoxia or C-2-ceramide. These results suggest that ceramide generated by activation of neutral magnesium-dependent sphingomyelinase mediates hypoxic cell death and that Bcl-2 has inhibitory effects on ceramide formation and caspase activation.
ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/11/20 alle ore 23:43:31