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Proteasome involvement and accumulation of ubiquitinated proteins in cerebellar granule neurons undergoing apoptosis.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Canu, Nadia Barbato, Christian Ciotti, Maria Teresa Serafino, Anna Lucia Calissano, Pietro |
| Copyright Year | 2000 |
| 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 trypsin-like 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 attributable to, 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 as a model system aimed at correlating these events with neurodegenerative diseases. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jneurosci.org/content/20/2/589.full.pdf |
| Alternate Webpage(s) | http://citeseerx.ist.psu.edu/viewdoc/download;jsessionid=BDBBFEC45A110164BF6F223204AEFE35?doi=10.1.1.335.4571&rep=rep1&type=pdf |
| PubMed reference number | 10632588v1 |
| Volume Number | 20 |
| Issue Number | 2 |
| Journal | The Journal of neuroscience : the official journal of the Society for Neuroscience |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Apoptosis CHYMOTRYPSIN Calpain Caspase Activation Caspase Inhibitors Cell Death Cessation of life Cortical Cell Layer of the Cerebellum Neurodegenerative Disorders Potassium Ubiquitin Ubiquitinated Proteins VAD I protocol benzyloxycarbonyl-Phe-Ala-fluormethylketone caspase-3 activity multicatalytic endopeptidase complex physical hard work |
| Content Type | Text |
| Resource Type | Article |
