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Titolo:
Role of PI 3-kinase, Akt and Bcl-2-related proteins in sustaining the survival of neurotrophic factor-independent adult sympathetic neurons
Autore:
Orike, N; Middleton, G; Borthwick, E; Buchman, V; Cowen, T; Davies, AM;
Indirizzi:
Royal Dick Sch Vet Studies, Dept Preclin Vet Sci, Edinburgh EH9 1QH, Midlothian, Scotland Royal Dick Sch Vet Studies Edinburgh Midlothian Scotland EH9 1QH Scotland Royal Free Hosp, Sch Med, Dept Anat & Dev Biol, London NW3 2PF, England Royal Free Hosp London England NW3 2PF Dev Biol, London NW3 2PF, England
Titolo Testata:
JOURNAL OF CELL BIOLOGY
fascicolo: 5, volume: 154, anno: 2001,
pagine: 995 - 1005
SICI:
0021-9525(20010903)154:5<995:ROP3AA>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
NERVE GROWTH-FACTOR; PROGRAMMED CELL-DEATH; NGF-MEDIATED SURVIVAL; NF-KAPPA-B; PHOSPHATIDYLINOSITOL 3-KINASE; CYTOCHROME-C; SENSORY NEURONS; BCL-X; TRANSCRIPTION FACTOR; SIGNAL-TRANSDUCTION;
Keywords:
phosphoinositide 3-kinase; Akt kinase/protein kinase B; bax; BcL-xL; signaling;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
82
Recensione:
Indirizzi per estratti:
Indirizzo: Davies, AM Royal Dick Sch Vet Studies, Dept Preclin Vet Sci, Summerhall Sq, EdinburghEH9 1QH, Midlothian, Scotland Royal Dick Sch Vet Studies Summerhall Sq Edinburgh Midlothian Scotland EH9 1QH
Citazione:
N. Orike et al., "Role of PI 3-kinase, Akt and Bcl-2-related proteins in sustaining the survival of neurotrophic factor-independent adult sympathetic neurons", J CELL BIOL, 154(5), 2001, pp. 995-1005

Abstract

By adulthood, sympathetic neurons have lost dependence on NGF and NT-3 andare able to survive in culture without added neurotrophic factors. To understand the molecular mechanisms that sustain adult neurons, we established low density glial cell-free cultures of 12-wk rat superior cervical ganglion neurons and manipulated the function and/or expression of key proteins implicated in regulating cell survival. Pharmacological inhibition of PI 3-kinase with LY294002 or Wortmannin killed these neurons, as did dominant-negative Class 1(A) PI 3-kinase, overexpression of Ruk(I) (a natural inhibitor of Class 1(A) PI 3-kinase), and dominant-negative Akt/PKB (a downstream effector of PI 3-kinase). Phospho-Akt was detectable in adult sympathetic neurons grown without neurotrophic factors and this was lost upon PI 3-kinase inhibition. The neurons died by a caspase-dependent mechanism after inhibition of PI 3-kinase, and were also killed by antisense Bcl-(XL) and antisenseBcl-2 or by overexpression of Bcl-(XS), Bad, and Bax. These results demonstrate that PI 3-kinase/Akt signaling and the expression of antiapoptotic members of the Bcl-2 family are required to sustain the survival of adult sympathetic neurons.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/11/20 alle ore 09:49:44