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Titolo:
A role for MAPK/ERK in sympathetic neuron survival: Protection against a p53-dependent, JNK-independent induction of apoptosis by cytosine arabinoside
Autore:
Anderson, CNG; Tolkovsky, AM;
Indirizzi:
Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England Univ Cambridge Cambridge England CB2 1QW hem, Cambridge CB2 1QW, England
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 2, volume: 19, anno: 1999,
pagine: 664 - 673
SICI:
0270-6474(19990115)19:2<664:ARFMIS>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
NERVE GROWTH-FACTOR; PROGRAMMED CELL-DEATH; KILLS POSTMITOTIC NEURONS; PROTEIN-KINASE; C-JUN; TUMOR-SUPPRESSOR; MAP KINASES; P53; ACTIVATION; NGF;
Keywords:
superior cervical ganglion neurons; MAPK/ERK; PKB/Akt; JNK; c-Jun phosphorylation; p53; CNTF; PD98059; signal transduction; DNA damage;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Tolkovsky, AM UnivQW,mbridge, Dept Biochem, Downing Site,Tennis Court Rd, Cambridge CB2 1 Univ Cambridge Downing Site,Tennis Court Rd Cambridge England CB2 1QW
Citazione:
C.N.G. Anderson e A.M. Tolkovsky, "A role for MAPK/ERK in sympathetic neuron survival: Protection against a p53-dependent, JNK-independent induction of apoptosis by cytosine arabinoside", J NEUROSC, 19(2), 1999, pp. 664-673

Abstract

The antimitotic nucleoside cytosine arabinoside (araC) causes apoptosis inpostmitotic neurons for which two mechanisms have been suggested: (1) aracdirectly inhibits a trophic factor-maintained signaling pathway required for survival, effectively mimicking trophic factor withdrawal; and (2) araC induces apoptosis by a p53-dependent mechanism distinct from trophic factorwithdrawal. in rat sympathetic neurons, we found that araC treatment for 12 hr induced similar to 25% apoptosis without affecting NGF-maintained signaling; there was neither reduction in the activity of mitogen actived protein kinase/extracellular signal-regulated kinase (MAPK/ERK) or protein kinase B/Akt, a kinase implicated in NGF-mediated survival, nor was there c-Jun N-terminal kinase (JNK) activation or c-Jun N-terminal phosphorylation, events implicated in apoptosis induced by NGF withdrawal. However, araC treatment, but not NGF-withdrawal, elevated expression of p53 protein before and during apoptosis. Additionally, araC-induced apoptosis was suppressed in sympathetic neurons from p53 null mice. Although MAPK/ERK activity is not necessary for NGF-induced survival, it protected against toxicity by araC, because inhibition of the MAPK pathway by PD98059 resulted in a significant increase in the rate of apoptosis induced by araC in the presence of NGF. Consistent with this finding, ciliary neurotrophic factor, which does not cause sustained activation of MAPK/ ERK, did not protect against araC toxicity. Our data show that, in contrast to NGF deprivation, arac induces apoptosisvia a p53-dependent, JNK-independent mechanism, against which MAPK/ERK plays a substantial protective role. Thus, NGF can suppress apoptotic mechanisms in addition to those caused by its own deprivation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 12:35:27