| pubmed-article:15569265 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15569265 | lifeskim:mentions | umls-concept:C0027882 | lld:lifeskim |
| pubmed-article:15569265 | lifeskim:mentions | umls-concept:C0162638 | lld:lifeskim |
| pubmed-article:15569265 | lifeskim:mentions | umls-concept:C0007765 | lld:lifeskim |
| pubmed-article:15569265 | lifeskim:mentions | umls-concept:C0010837 | lld:lifeskim |
| pubmed-article:15569265 | lifeskim:mentions | umls-concept:C0026187 | lld:lifeskim |
| pubmed-article:15569265 | lifeskim:mentions | umls-concept:C1366876 | lld:lifeskim |
| pubmed-article:15569265 | lifeskim:mentions | umls-concept:C1833235 | lld:lifeskim |
| pubmed-article:15569265 | lifeskim:mentions | umls-concept:C1704259 | lld:lifeskim |
| pubmed-article:15569265 | lifeskim:mentions | umls-concept:C0443199 | lld:lifeskim |
| pubmed-article:15569265 | lifeskim:mentions | umls-concept:C1705987 | lld:lifeskim |
| pubmed-article:15569265 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:15569265 | lifeskim:mentions | umls-concept:C1292733 | lld:lifeskim |
| pubmed-article:15569265 | pubmed:issue | 5 | lld:pubmed |
| pubmed-article:15569265 | pubmed:dateCreated | 2004-11-30 | lld:pubmed |
| pubmed-article:15569265 | pubmed:abstractText | Minocycline has been shown to have remarkably neuroprotective qualities, but underlying mechanisms remain elusive. We reported here the robust neuroprotection by minocycline against glutamate-induced apoptosis through regulations of p38 and Akt pathways. Pre-treatment of cerebellar granule neurons (CGNs) with minocycline (10-100 microm) elicited a dose-dependent reduction of glutamate excitotoxicity and blocked glutamate-induced nuclear condensation and DNA fragmentations. Using patch-clamping and fluorescence Ca2+ imaging techniques, it was found that minocycline neither blocked NMDA receptors, nor reduced glutamate-caused rises in intracellular Ca2+. Instead, confirmed by immunoblots, minocycline in vivo and in vitro was shown to directly inhibit the activation of p38 caused by glutamate. A p38-specific inhibitor, SB203580, also attenuated glutamate excitotoxicity. Furthermore, the neuroprotective effects of minocycline were blocked by phosphatidylinositol 3-kinase (PI3-K) inhibitors LY294002 and wortmannin, while pharmacologic inhibition of glycogen synthase kinase 3beta (GSK3beta) attenuated glutamate-induced apoptosis. In addition, immunoblots revealed that minocycline reversed the suppression of phosphorylated Akt and GSK3beta caused by glutamate, as were abolished by PI3-K inhibitors. These results demonstrate that minocycline prevents glutamate-induced apoptosis in CGNs by directly inhibiting p38 activity and maintaining the activation of PI3-K/Akt pathway, which offers a novel modality as to how the drug exerts protective effects. | lld:pubmed |
| pubmed-article:15569265 | pubmed:language | eng | lld:pubmed |
| pubmed-article:15569265 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15569265 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:15569265 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15569265 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15569265 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15569265 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15569265 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15569265 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15569265 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15569265 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15569265 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15569265 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15569265 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15569265 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15569265 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15569265 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15569265 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15569265 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15569265 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15569265 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15569265 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15569265 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15569265 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15569265 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15569265 | pubmed:month | Dec | lld:pubmed |
| pubmed-article:15569265 | pubmed:issn | 0022-3042 | lld:pubmed |
| pubmed-article:15569265 | pubmed:author | pubmed-author:SucherNikolau... | lld:pubmed |
| pubmed-article:15569265 | pubmed:author | pubmed-author:PuYongmeiY | lld:pubmed |
| pubmed-article:15569265 | pubmed:author | pubmed-author:ChangDonald... | lld:pubmed |
| pubmed-article:15569265 | pubmed:author | pubmed-author:ChanLing... | lld:pubmed |
| pubmed-article:15569265 | pubmed:author | pubmed-author:LiMingtaoM | lld:pubmed |
| pubmed-article:15569265 | pubmed:author | pubmed-author:LiWenmingW | lld:pubmed |
| pubmed-article:15569265 | pubmed:author | pubmed-author:HanYifanY | lld:pubmed |
| pubmed-article:15569265 | pubmed:author | pubmed-author:PiRongbiaoR | lld:pubmed |
| pubmed-article:15569265 | pubmed:author | pubmed-author:LeeNelson T... | lld:pubmed |
| pubmed-article:15569265 | pubmed:author | pubmed-author:ChanHugh H... | lld:pubmed |
| pubmed-article:15569265 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15569265 | pubmed:volume | 91 | lld:pubmed |
| pubmed-article:15569265 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15569265 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15569265 | pubmed:pagination | 1219-30 | lld:pubmed |
| pubmed-article:15569265 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
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| pubmed-article:15569265 | pubmed:meshHeading | pubmed-meshheading:15569265... | lld:pubmed |
| pubmed-article:15569265 | pubmed:year | 2004 | lld:pubmed |
| pubmed-article:15569265 | pubmed:articleTitle | Minocycline prevents glutamate-induced apoptosis of cerebellar granule neurons by differential regulation of p38 and Akt pathways. | lld:pubmed |
| pubmed-article:15569265 | pubmed:affiliation | Department of Biochemistry, Hong Kong University of Science & Technology, Clear Water Bay, Kowloon, Hong Kong, China. | lld:pubmed |
