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Titolo:
Proteasome involvement and accumulation of ubiquitinated proteins in cerebellar granule neurons undergoing apoptosis
Autore:
Canu, N; Barbato, C; Ciotti, MT; Serafino, A; Dus, L; Calissano, P;
Indirizzi:
CNR, Ist Neurobiol, I-00137 Rome, Italy CNR Rome Italy I-00137CNR, Ist Neurobiol, I-00137 Rome, Italy Univ Roma Tor Vergata, Fac Med & Chirurg, Dipartimento Neurosci, I-00133 Rome, Italy Univ Roma Tor Vergata Rome Italy I-00133 o Neurosci, I-00133 Rome, Italy CNR, Area Ric Roma, I-00133 Rome, Italy CNR Rome Italy I-00133CNR, Area Ric Roma, I-00133 Rome, Italy
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 2, volume: 20, anno: 2000,
pagine: 589 - 599
SICI:
0270-6474(20000115)20:2<589:PIAAOU>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROGRAMMED CELL-DEATH; DEUBIQUITINATING ENZYMES; POLYUBIQUITIN CHAINS; THYMOCYTE APOPTOSIS; ALZHEIMERS-DISEASE; ISOPEPTIDASE-T; ICE-LIKE; DEGRADATION; INHIBITION; ACTIVATION;
Keywords:
apoptosis; neurodegeneration; ubiquitin-protein conjugates; proteasome activity; deubiquitinating activity; cerebellar granule neurons;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
64
Recensione:
Indirizzi per estratti:
Indirizzo: Canu, N CNR, Ist Neurobiol, Vle Marx 15, I-00137 Rome, Italy CNR Vle Marx 15 Rome Italy I-00137 e Marx 15, I-00137 Rome, Italy
Citazione:
N. Canu et al., "Proteasome involvement and accumulation of ubiquitinated proteins in cerebellar granule neurons undergoing apoptosis", J NEUROSC, 20(2), 2000, pp. 589-599

Abstract

We investigated the potential role of the ubiquitin proteolytic system in the death of cerebellar granule neurons induced by reduction of extracellular potassium. Inhibitors of proteasomal function block apoptosis if administered at onset of this process, but they do not exert such effect when added 2-3 hr later. The same inhibitors also prevent caspase-3 activity and calpain-caspase-3-mediated processing of tau protein, suggesting that proteasomes are involved upstream of the caspase activation. Although the proteasomes seem to play an early primary role in programmed cell death, we found that with progression of apoptosis, during the execution phase, a perturbation in normal ubiquitin-proteasome function occurs, and high levels of ubiquitinated proteins accumulate in the cytoplasm of dying cells. Such accumulation correlates with a progressive decline of proteasome chymotrypsin and trypsinlike activities and, to a lower extent, of postacidic-like activity. Both intracytoplasmic accumulation of ubiquitinated proteins and decline of proteasome function are reversed by the pan-caspase inhibitor Z-VAD-fmk. The decline in proteasome function is accompanied by, and likely attributableto, a marked and progressive decline of deubiquitinating activities. The finding that the proteasomes are early involved in apoptosis and that ubiquitinated proteins accumulate during this process prospect granule neurons asa model system aimed at correlating these events with neurodegenerative diseases.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/09/20 alle ore 13:35:35