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Titolo:
p53 regulates ceramide formation by neutral sphingomyelinase through reactive oxygen species in human glioma cells
Autore:
Sawada, M; Nakashima, S; Kiyono, T; Nakagawa, M; Yamada, J; Yamakawa, H; Banno, Y; Shinoda, J; Nishimura, Y; Nozawa, Y; Sakai, N;
Indirizzi:
Gifu Univ, Sch Med, Dept Neurosurg, Gifu 5008705, Japan Gifu Univ Gifu Japan 5008705 ch Med, Dept Neurosurg, Gifu 5008705, Japan Gifu Univ, Sch Med, Dept Biochem, Gifu 5008705, Japan Gifu Univ Gifu Japan 5008705 Sch Med, Dept Biochem, Gifu 5008705, Japan Aichi Canc Ctr, Lab Viral Oncol, Chikusa Ku, Nagoya, Aichi 4648681, Japan Aichi Canc Ctr Nagoya Aichi Japan 4648681 u, Nagoya, Aichi 4648681, Japan Gifu Int Inst Biotechnol, Mitake, Gifu 5050116, Japan Gifu Int Inst Biotechnol Mitake Gifu Japan 5050116 e, Gifu 5050116, Japan
Titolo Testata:
ONCOGENE
fascicolo: 11, volume: 20, anno: 2001,
pagine: 1368 - 1378
SICI:
0950-9232(20010315)20:11<1368:PRCFBN>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
WILD-TYPE P53; HUMAN PAPILLOMAVIRUS TYPE-16; HUMAN EPITHELIAL-CELLS; INDUCED APOPTOSIS; HYDROGEN-PEROXIDE; P53-INDUCED APOPTOSIS; CASPASE ACTIVATION; GROWTH ARREST; DEATH; INHIBITION;
Keywords:
ceramide; glioma; neutral sphingomyelinase; p53; reactive oxygen species;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Sawada, M Gifu Univ, Sch Med, Dept Neurosurg, Tsukasamachi 40, Gifu 5008705, Japan Gifu Univ Tsukasamachi 40 Gifu Japan 5008705 ifu 5008705, Japan
Citazione:
M. Sawada et al., "p53 regulates ceramide formation by neutral sphingomyelinase through reactive oxygen species in human glioma cells", ONCOGENE, 20(11), 2001, pp. 1368-1378

Abstract

The present study was designed to elucidate the relationship between p53 and ceramide, both of which are involved in apoptotic signaling, Treatment of human glioma cells with etoposide caused apoptosis only in cells expressing functional p53. p53 activation was followed by the formation of reactiveoxygen species (ROS), superoxide anion (O-2(-.)) measured by hydroethidiumoxidation into ethidium and hydrogen peroxide (H2O2) measured by oxidationof 2',7'-dichlorofluorescin (DCFH) into 2',7'-dichlorofluorescein (DCF), which was accompanied with ceramide generation through the activation of neutral, but not acid, sphingomyelinase. Superoxide dismutase (SOD), a selective antioxidant for O-2(-.) had no effects on p53 expression but inhibited ceramide generation and apoptotic cell death caused by etoposide, However, catalase, a specific antioxidant for H2O2, only weakly inhibited and sodium formate, a hydroxyl radical ((OH)-O-.) scavenger, unaffected etoposide-induced apoptosis, Like etoposide-induced cell death, treatment of glioma cellswith the O-2(-.)-releasing agent, pyrogallol, induced typical apoptosis and ceramide generation even in the presence of catalase, In contrast, human glioma cells lacking functional p53, either due to mutation or the expression of E6 protein of human papillomavirus, were highly resistant to etoposide and exhibited no significant change in the ceramide level. Moreover, expression of functional p53 protein in glioma cells expressing mutant p53 using a temperature-sensitive human p53(Val138) induced ceramide accumulation by the activation of neutral sphingomyelinase which was dependent on the generation of O-2(-.), Taken together, these results suggest that p53 may modulate ceramide generation by activation of neutral sphingomyelinase through the formation of O-2(-.), but not its downstream compounds H2O2 or (OH)-O-..

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/07/20 alle ore 11:20:02