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Titolo:
CEP-1347 (KT7515), an inhibitor of JNK activation, rescues sympathetic neurons and neuronally differentiated PC12 cells from death evoked by three distinct insults
Autore:
Maroney, AC; Finn, JP; Bozyczko-Coyne, D; OKane, TM; Neff, NT; Tolkovsky, AM; Park, DS; Yan, CYI; Troy, CM; Greene, LA;
Indirizzi:
Cephalon, W Chester, PA USA Cephalon W Chester PA USACephalon, W Chester, PA USA Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA Columbia Univ Coll Phys & Surg New York NY USA 10032 w York, NY 10032 USA Columbia Univ Coll Phys & Surg, Ctr Neurobiol & Behav, New York, NY 10032 USA Columbia Univ Coll Phys & Surg New York NY USA 10032 w York, NY 10032 USA Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England Univ Cambridge Cambridge England CB2 1QW hem, Cambridge CB2 1QW, England
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 5, volume: 73, anno: 1999,
pagine: 1901 - 1912
SICI:
0022-3042(199911)73:5<1901:C(AIOJ>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
NERVE GROWTH-FACTOR; N-TERMINAL KINASE; STRESS-INDUCED APOPTOSIS; TROPHIC FACTOR WITHDRAWAL; C-JUN; PROTEIN-KINASE; NEURITE OUTGROWTH; OXIDATIVE STRESS; DOWN-REGULATION; SIGNALING PATHWAY;
Keywords:
CEP-1347; c-Jun N-terminal kinase; sympathetic neurons; PC12 cells; apoptosis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
73
Recensione:
Indirizzi per estratti:
Indirizzo: Maroney, AC 145 Brandywine Pkwy, W Chester, PA 19380 USA 145 Brandywine Pkwy W Chester PA USA 19380 ster, PA 19380 USA
Citazione:
A.C. Maroney et al., "CEP-1347 (KT7515), an inhibitor of JNK activation, rescues sympathetic neurons and neuronally differentiated PC12 cells from death evoked by three distinct insults", J NEUROCHEM, 73(5), 1999, pp. 1901-1912

Abstract

The c-Jun N-terminal kinase signaling cascade appears to play a role in some cases of cell death, including neuronal apoptosis. CEP-1347 (KT7515), anindolocarbazole of the K252a family, blocks this stress signaling cascade and promotes survival. Here, we used CEP-1347 to probe whether neuronal death pathways activated by distinct insults also possess elements in common. Cultured rat sympathetic neurons and neuronally differentiated PC12 cells were induced to die by withdrawal of nerve growth factor, exposure to ultraviolet irradiation, or subjection to oxidative stress. In each case, death was prevented by 100-200 nM CEP-1347. Moreover, in each of these death paradigms, c-Jun N-terminal kinase 1 activity in neuronally differentiated PC12 cells was elevated by two- or threefold, and this increase was totally blocked by CEP-1347 at concentrations that promoted survival. In contrast, 200 nM CEP-1347 did not block death due to serum withdrawal from undifferentiated PC12 cells or to activation of Fas in Jurkat T cell cultures, even though in each case c-Jun N-terminal kinase 1 activation occurred and was inhibited by CEP-1347. These observations suggest that some but not all death pathways triggered by different insults can include a common mechanistic component, a likely candidate for which is activation of the c-Jun N-terminal kinase signaling cascade.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/07/20 alle ore 08:45:20