| Neurotrophin-3 reduces apoptosis induced by 6-OHDA in PC12 cells through Akt signaling pathway. | |
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MedLine Citation:
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PMID: 18462913 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Previous work has demonstrated that 6-hydroxydopamine (6-OHDA) induces apoptosis in PC12 cells. The goal of the present study was to investigate the mechanisms underlying the protection by neurotrophin-3 (NT-3) against 6-OHDA-induced apoptosis in PC12 cells. Treatment of PC12 cells with 6-OHDA resulted in activation of caspase-3 and subsequent apoptosis, as detected by TUNEL staining. In addition, Akt phosphorylation was decreased following 6-OHDA treatment. Pretreatment with NT-3 reduced the percentage of apoptotic cells and caspase-3 activity induced by 6-OHDA and suppressed the cleavage of caspase-3 and Poly(ADP-ribose) polymerase (PARP) with a significant decrease in cell viability. Moreover, Akt phosphorylation was enhanced and 6-OHDA-induced chromatin condensation was suppressed by NT-3. Such NT-3-evoked suppression in chromatin condensation was reversed by anti-TrkA antibody receptor blockade. Further study revealed that LY294002, an inhibitor of PI3-kinase (a molecule upstream of Akt), enhanced 6-OHDA-induced apoptosis. These data indicate that NT-3 prevents 6-OHDA-induced apoptosis in PC12 cells via activation of PI3-kinase/Akt pathway. |
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Authors:
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Zhiquan Li; Yunyu Hu; Qingsheng Zhu; Jinyu Zhu |
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Publication Detail:
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Type: Journal Article Date: 2008-04-04 |
Journal Detail:
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Title: International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience Volume: 26 ISSN: 0736-5748 ISO Abbreviation: Int. J. Dev. Neurosci. Publication Date: 2008 Oct |
Date Detail:
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Created Date: 2008-07-21 Completed Date: 2008-11-05 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8401784 Medline TA: Int J Dev Neurosci Country: England |
Other Details:
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Languages: eng Pagination: 635-40 Citation Subset: IM |
Affiliation:
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PLA Institute of Othropadics & Traumatology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic Agents
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toxicity* Animals Apoptosis / drug effects* Caspase 3 / metabolism Chromones / pharmacology Drug Interactions Enzyme Inhibitors / pharmacology Flow Cytometry / methods Morpholines / pharmacology Neurotrophin 3 / pharmacology* Oxidopamine / toxicity* PC12 Cells / drug effects Poly(ADP-ribose) Polymerases / metabolism Proto-Oncogene Proteins c-akt / metabolism* Rats Signal Transduction / drug effects* |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic Agents; 0/Chromones; 0/Enzyme Inhibitors; 0/Morpholines; 0/Neurotrophin 3; 1199-18-4/Oxidopamine; 154447-36-6/2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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