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Titolo:
NGF-withdrawal induces apoptosis in pancreatic beta cells in vitro
Autore:
Pierucci, D; Cicconi, S; Bonini, P; Ferrelli, F; Pastore, D; Matteucci, C; Marselli, L; Marchetti, P; Ris, F; Halban, P; Oberholzer, J; Federici, M; Cozzolino, F; Lauro, R; Borboni, P; Marlier, LNJL;
Indirizzi:
Univ Roma Tor Vergata, Dept Internal Med, Mol Med Lab, I-00133 Rome, ItalyUniv Roma Tor Vergata Rome Italy I-00133 ol Med Lab, I-00133 Rome, Italy Univ Roma Tor Vergata, Dept Expt Med & Biochem Sci, I-00133 Rome, Italy Univ Roma Tor Vergata Rome Italy I-00133 iochem Sci, I-00133 Rome, Italy Univ Pisa, Dept Endocrinol & Metab, I-56100 Pisa, Italy Univ Pisa Pisa Italy I-56100 ept Endocrinol & Metab, I-56100 Pisa, Italy Univ Geneva, Med Ctr, Louis Jeantet Res Labs, CH-1211 Geneva, Switzerland Univ Geneva Geneva Switzerland CH-1211 Labs, CH-1211 Geneva, Switzerland Clin Digest Surg, Div Surg Invest, Geneva, Switzerland Clin Digest Surg Geneva Switzerland iv Surg Invest, Geneva, Switzerland CNR, Inst Neourosci & Mol Med, Rome, Italy CNR Rome ItalyCNR, Inst Neourosci & Mol Med, Rome, Italy
Titolo Testata:
DIABETOLOGIA
fascicolo: 10, volume: 44, anno: 2001,
pagine: 1281 - 1295
SICI:
0012-186X(200110)44:10<1281:NIAIPB>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
NERVE GROWTH-FACTOR; ACTIVATED PROTEIN-KINASE; HIGH-AFFINITY RECEPTOR; P75 NEUROTROPHIN RECEPTOR; DEATH AGONIST BAD; SYMPATHETIC NEURONS; PHOSPHATIDYLINOSITOL 3-KINASE; PC12 CELLS; SIGNAL-TRANSDUCTION; ACID DECARBOXYLASE;
Keywords:
islet cell; nerve growth factor; nerve growth factor receptors; diabetes mellitus; apoptosis; cell death; protein-tyrosine kinase; proto-oncogene proteins c-bcl-2; signal transduction; phosphorylation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
85
Recensione:
Indirizzi per estratti:
Indirizzo: Marlier, LNJL Univ Roma Tor Vergata, Dept Internal Med, Mol Med Lab, Via Tor Vergata 135, I-00133 Rome, Italy Univ Roma Tor Vergata Via Tor Vergata 135 Rome Italy I-00133
Citazione:
D. Pierucci et al., "NGF-withdrawal induces apoptosis in pancreatic beta cells in vitro", DIABETOLOG, 44(10), 2001, pp. 1281-1295

Abstract

Aims/hypothesis. Using primary cultures of human pancreatic islets, purified human pancreatic beta cells and the mouse beta TC6-F7 cell line, we analysed the expression of nerve growth factor, (NGF/NGF) receptors in beta cells. To investigate whether NGF could sub-serve an autocrine antiapoptotic role in beta cells, we studied the effects of NGF withdrawal using a neutralizing monoclonal anti-NGF antibody. Methods. The expression of NGF and NGF receptors (gp140(Trk-A) and p75(NTR)) were analysed by RT-PCR and immunofluorescence. Pulse-chase experiments and beta cell/PC12 co-cultures were used to investigate NGF production and secretion from beta cells. Possible apoptosis induced by NGF withdrawal wasmonitored by phosphatidylserine translocation, nucleosomal formation, DNA laddering and FACS analysis. Involvement of transcription/translation mechanisms were investigated as well as the gp140(Trk-A) required. Finally, signal transduction pathways typically involved in apoptotic mechanisms were analysed by western blot analysis. Results. We show that NGF and both NGF receptors, gp140(Trk-A) and p75(NTR) are expressed in beta cells where NGF is produced and secreted in a biologically active form. NGF-withdrawal induces beta-cell transcription/translation independent apoptosis but mediated by gp140Trk-A. Analysis of signal transduction pathways revealed that NGF withdrawal inhibits the PI3-K, protein kinase B (AKT), Bad survival pathway and activates c-Jun kinase (JNK) whereas ERKs and p38 mitogen-activated protein kinase (MAPK) are not affected. Moreover, Bcl-XL, but not Bcl-2 protein expression are reduced. Conclusion/interpretation. We suggest that the integrity of the NGF/NGF receptor system and NGF bioavailability participate in controlling beta-cell survival in culture which represents a key issue for improving possibilities for transplantations in the treatment of diabetes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/09/20 alle ore 15:38:16