| Autor: |
Hao Liu, Wenjin Li, Muzamil Ahmad, Tricia M. Miller, Marie E. Rose, Samuel M. Poloyac, Guy Uechi, Manimalha Balasubramani, Robert W. Hickey, Steven H. Graham |
| Jazyk: |
angličtina |
| Rok vydání: |
2011 |
| Předmět: |
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| Zdroj: |
Neurobiology of Disease, Vol 41, Iss 2, Pp 318-328 (2011) |
| Druh dokumentu: |
article |
| ISSN: |
1095-953X |
| DOI: |
10.1016/j.nbd.2010.09.020 |
| Popis: |
Cyclopentenone prostaglandins (CyPGs), such as 15-deoxy-Δ12,14 -prostaglandin J2 (15d-PGJ2), are active prostaglandin metabolites exerting a variety of biological effects that may be important in the pathogenesis of neurological diseases. Ubiquitin-C-terminal hydrolase L1 (UCH-L1) is a brain specific deubiquitinating enzyme whose aberrant function has been linked to neurodegenerative disorders. We report that [15d-PGJ2] detected by quadrapole mass spectrometry (MS) increases in rat brain after temporary focal ischemia, and that treatment with 15d-PGJ2 induces accumulation of ubiquitinated proteins and exacerbates cell death in normoxic and hypoxic primary neurons. 15d-PGJ2 covalently modifies UCH-L1 and inhibits its hydrolase activity. Pharmacologic inhibition of UCH-L1 exacerbates hypoxic neuronal death while transduction with a TAT–UCH-L1 fusion protein protects neurons from hypoxia. These studies indicate that UCH-L1 function is important in hypoxic neuronal death and that excessive production of CyPGs after stroke may exacerbate ischemic injury by modification and inhibition of UCH-L1. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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