The mechanism of t-butylhydroperoxide-induced apoptosis in IMR-32 human neuroblastoma cells
The Korean Journal of Physiology and Pharmacology
;
: 19-28, 1999.
Article
Dans Anglais
| WPRIM
| ID: wpr-728037
ABSTRACT
Apoptosis has been implicated in the pathophysiological mechanisms of various neurodegenerative diseases. In a variety of cell types, oxidative stress has been demonstrated to play an important role in the apoptotic cell death. However, the exact mechanism of oxidative stress-induced apoptosis in neuronal cells is not known. In this study, we induced oxidative stress in IMR-32 human neuroblastoma cells with tert-butylhydroperoxide (TBHP), which was confirmed by significantly reduced glutathione content and glutathione reductase activity, and increased glutathione peroxidase activity. TBHP induced decrease in cell viability and increase in DNA fragmentation, a hallmark of apoptosis, in a dose-dependent manner. TBHP also induced a sustained increase in intracellular Ca2+ concentration, which was completely prevented either by EGTA, an extracellular Ca2+ chelator or by flufenamic acid (FA), a non-selective cation channel (NSCC) blocker. These results indicate that the TBHP-induced intracellular Ca2+ increase may be due to Ca2+ influx through the activation of NSCCs. In addition, treatment with either an intracellular Ca2+ chelator (BAPTA/AM) or FA significantly suppressed the TBHP-induced apoptosis. Moreover, TBHP increased the expression of p53 gene but decreased c-myc gene expression. Taken together, these results suggest that the oxidative stress-induced apoptosis in neuronal cells may be mediated through the activation of intracellular Ca2+ signals and altered expression of p53 and c-myc.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Survie cellulaire
/
Acide flufénamique
/
Gènes myc
/
Gènes p53
/
Mort cellulaire
/
Acide egtazique
/
Apoptose
/
Stress oxydatif
/
Maladies neurodégénératives
/
2-Hydroperoxy-2-méthyl-propane
Limites du sujet:
Humains
langue:
Anglais
Texte intégral:
The Korean Journal of Physiology and Pharmacology
Année:
1999
Type:
Article
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