Document Detail


Minocycline protects PC12 cells against NMDA-induced injury via inhibiting 5-lipoxygenase activation.
MedLine Citation:
PMID:  16574083     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
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:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-03-30
Journal Detail:
Title:  Brain research     Volume:  1085     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-05-22     Completed Date:  2006-08-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  57-67     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310031, PR China.
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MeSH Terms
Descriptor/Qualifier:
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:
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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