Document Detail

Melatonin attenuates 1-methyl-4-phenylpyridinium-induced PC12 cell death.
MedLine Citation:
PMID:  15659124     Owner:  NLM     Status:  MEDLINE    
AIM: To explore the effect of melatonin on PC12 cell death induced by 1-methyl-4-phenylpyridinium (MPP+). METHODS: MTT assay, lactate dehydrogenase (LDH) efflux assay, and immunohistochemistry methods were used to measure neurotoxicity of PC12 cells treated acutely with MPP+ in low glucose and high glucose conditions, and to assess the neuroprotective effect of melatonin on PC12 cell death induced by MPP+. RESULTS: In a low glucose condition, MPP+ significantly induced PC12 cell death, which showed time and concentration dependence. In a serum-free low glucose condition, the percentages of viability of cells treated with MPP+ for 12, 24, 48, 72, and 96 h were 85.1%, 75.4%, 64.9%, 28.15%, and 9%, respectively. The level of LDH in the culture medium increased and tyrosine hydroxylase positive (TH+) cell count decreased. However, in a serum-free high glucose condition, MPP+ did not significantly induce PC12 cell death compared with control at various concentrations and time regimens. When the cells were preincubated with melatonin 250 micromol/L for 48, 72, and 96 h in a serum-free low glucose condition, cell survival rate significantly increased to 78.1%, 58.8%, and 31.6%, respectively. Melatonin abolished the LDH leakage of cells treated with MPP+ and increased TH+ cells count. CONCLUSION: MPP+ caused concentration-dependent PC12 cell death. The level of glucose was an important factor to MPP+ induced dopaminergic PC12 cell death. Low glucose level could potentiate MPP+ toxicity, while high glucose level could reduce the toxicity. In addition, melatonin attenuated PC12 cell death induced by MPP+.
Jin-feng Bao; Ren-gang Wu; Xiao-ping Zhang; Yan Song; Chang-ling Li
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Acta pharmacologica Sinica     Volume:  26     ISSN:  1671-4083     ISO Abbreviation:  Acta Pharmacol. Sin.     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2005-01-20     Completed Date:  2005-06-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100956087     Medline TA:  Acta Pharmacol Sin     Country:  England    
Other Details:
Languages:  eng     Pagination:  117-23     Citation Subset:  IM    
Department of Pharmacology, School of Pharmaceutical Sciences, Beijing 100083, China.
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MeSH Terms
1-Methyl-4-phenylpyridinium / antagonists & inhibitors*,  toxicity
Cell Death / drug effects
Cell Survival / drug effects
Culture Media, Serum-Free
Glucose / administration & dosage,  pharmacology*
L-Lactate Dehydrogenase / metabolism
Melatonin / pharmacology*
Neuroprotective Agents / pharmacology*
PC12 Cells / drug effects,  metabolism
Tyrosine 3-Monooxygenase / metabolism
Reg. No./Substance:
0/Culture Media, Serum-Free; 0/Neuroprotective Agents; 48134-75-4/1-Methyl-4-phenylpyridinium; 50-99-7/Glucose; 73-31-4/Melatonin; EC Dehydrogenase; EC 3-Monooxygenase

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