| Minocycline protects PC12 cells against NMDA-induced injury via inhibiting 5-lipoxygenase activation. | |
MedLine Citation:
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PMID: 16574083 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Recently, we have reported that minocycline, a semi-synthetic tetracycline with neuroprotective effects, inhibits the in vitro ischemic-like injury and 5-lipoxygenase (5-LOX) activation in PC12 cells. In the present study, we further determined whether minocycline protects PC12 cells from excitotoxicity via inhibiting 5-LOX activation. We used N-methyl-d-aspartate (NMDA, 200 microM) to induce early (exposure for 6 h) and delayed (exposure for 6 h followed by 24 h recovery) injuries. We found that NMDA receptor antagonist ketamine, 5-LOX inhibitor caffeic acid and minocycline concentration dependently attenuated NMDA-induced early and delayed cell injuries (viability reduction and cell death). However, only ketamine (1 microM) inhibited NMDA-evoked elevation of intracellular calcium. In addition, immunohistochemical analysis showed that NMDA induced 5-LOX translocation to the nuclear membrane after 1- to 6-h exposure which was confirmed by Western blotting, indicating that 5-LOX was activated. Ketamine, caffeic acid and minocycline (each at 1 microM) inhibited 5-LOX translocation after early injury. After delayed injury, PC12 cells were shrunk, and 5-LOX was translocated to the nuclei and nuclear membrane; ketamine, caffeic acid and minocycline inhibited both cell shrinking and 5-LOX translocation. As a control, 12-LOX inhibitor baicalein showed a weak effect on cell viability and death, but no effect on 5-LOX translocation. Therefore, we conclude that the protective effect of minocycline on NMDA-induced injury is partly mediated by inhibiting 5-LOX activation. |
Authors:
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Ying Song; Er-Qing Wei; Wei-Ping Zhang; Qiu-Fu Ge; Jian-Ren Liu; Meng-Ling Wang; Xiao-Jia Huang; Xin Hu; Zhong Chen |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2006-03-30 |
Journal Detail:
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Title: Brain research Volume: 1085 ISSN: 0006-8993 ISO Abbreviation: Brain Res. Publication Date: 2006 Apr |
Date Detail:
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Created Date: 2006-05-22 Completed Date: 2006-08-10 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0045503 Medline TA: Brain Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 57-67 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310031, PR China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Arachidonate 5-Lipoxygenase / physiology* Blotting, Western / methods Calcium / metabolism Dose-Response Relationship, Drug Drug Interactions Enzyme Activation / drug effects Enzyme Inhibitors / pharmacology Excitatory Amino Acid Agonists / toxicity* Excitatory Amino Acid Antagonists / pharmacology Flavanones / pharmacology Immunohistochemistry / methods Ketamine / pharmacology Minocycline / pharmacology* N-Methylaspartate / toxicity* Neuroprotective Agents / pharmacology* PC12 Cells / drug effects*, pathology Rats Tetrazolium Salts / diagnostic use Thiazoles / diagnostic use Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Excitatory Amino Acid Agonists; 0/Excitatory Amino Acid Antagonists; 0/Flavanones; 0/Neuroprotective Agents; 0/Tetrazolium Salts; 0/Thiazoles; 10118-90-8/Minocycline; 298-93-1/thiazolyl blue; 491-67-8/baicalein; 6384-92-5/N-Methylaspartate; 6740-88-1/Ketamine; 7440-70-2/Calcium; EC 1.13.11.34/Arachidonate 5-Lipoxygenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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