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Titolo:
p53-dependent radiation-induced crypt intestinal epithelial cells apoptosis is mediated in part through TNF-TNFR1 system
Autore:
Inagaki-Ohara, K; Yada, S; Takamura, N; Reaves, M; Yu, XH; Liu, ER; Rooney, I; Nicholas, S; Castro, A; Ware, CF; Green, DR; Lin, T;
Indirizzi:
Northwestern Univ, Sch Med, Dept Med, Gastroenterol Sect, Chicago, IL 60611 USA Northwestern Univ Chicago IL USA 60611 nterol Sect, Chicago, IL 60611 USA La Jolla Inst Allergy & Immunol, Div Cellular Immunol, San Diego, CA 92121USA La Jolla Inst Allergy & Immunol San Diego CA USA 92121 Diego, CA 92121USA La Jolla Inst Allergy & Immunol, Div Mol Immunol, San Diego, CA 92121 USA La Jolla Inst Allergy & Immunol San Diego CA USA 92121 iego, CA 92121 USA
Titolo Testata:
ONCOGENE
fascicolo: 7, volume: 20, anno: 2001,
pagine: 812 - 818
SICI:
0950-9232(20010215)20:7<812:PRCIEC>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; FAS LIGAND EXPRESSION; VERSUS-HOST DISEASE; IN-VIVO; INTRAEPITHELIAL LYMPHOCYTES; GASTROINTESTINAL-TRACT; IONIZING-RADIATION; GAMMA-IRRADIATION; DNA DAMAGE;
Keywords:
apoptosis; intestinal epithelial cells; p53; TNF;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Lin, T Northwestern Univ, Sch Med, Dept Med, Gastroenterol Sect, Chicago, IL 60611 USA Northwestern Univ Chicago IL USA 60611 Sect, Chicago, IL 60611 USA
Citazione:
K. Inagaki-Ohara et al., "p53-dependent radiation-induced crypt intestinal epithelial cells apoptosis is mediated in part through TNF-TNFR1 system", ONCOGENE, 20(7), 2001, pp. 812-818

Abstract

Radiation induces apoptosis of crypt intestinal epithelial cells (IEC) through a pathway that is largely dependent on p53. However, exactly how p53 mediates IEC apoptosis is unclear, Studies irt vitro suggest that one mechanism by which p53 mediates apoptosis is through its ability to transactivatemembers of the TNF receptor family of (Death Receptors', Here, we examinedthe role of one of its member, TNF receptor type 1 (TNFR1), in an in viva model of p53-dependent radiation-induced LEC apoptosis, We demonstrate thatmice genetically engineered to be deficient in TNF receptor type 1 (TNFR1(-/-)) and mice injected with TNFR1-fusion chimeric protein (TNFR1-Fc; a competitive inhibitor of TNFR1) were partially protected (30-40%) from p53-dependent radiation-induced IEC apoptosis, However, we found no evidence to support the possibility p53 transcriptionally regulates the expression of TNFR1 nor increases the susceptibility of TEC to TNF-mediated apoptosis, Interestingly, we found that injection of TNF readily induced LEC apoptosis and that radiation induced a p53-dependent increase in the intestinal level of TNF. Furthermore, injection of a neutralizing anti-TNF mAb reduced p53-dependent radiation-induced IEC apoptosis by approximately 60%. Overall, these results suggest that p53-dependent radiation-induced IEC apoptosis is mediated in part through ability of p53 to regulate TNF, which subsequently induces IEC apoptosis through TNFR1.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 14:17:55