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Published on: January 7, 2014
Melatonin attenuates 1-methyl-4-phenylpyridinium-induced PC12 cell death
Jin-feng Bao1, Ren-gang Wu, Xiao-ping Zhang
1Department of Pharmacology, School of Pharmaceutical Sciences, Beijing 100083, China. srgltlsn93@hotmail.com
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+.
Insights
Melatonin protects PC12 cells from 1-methyl-4-phenylpyridinium (MPP+) induced death. Glucose levels significantly impact MPP+ toxicity, with low glucose potentiating cell death, while high glucose offers protection.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- 1-methyl-4-phenylpyridinium (MPP+) is a neurotoxin used to model Parkinson's disease.
- PC12 cells are a neuronal cell line commonly used in neurotoxicity studies.
- Glucose metabolism plays a critical role in neuronal health and vulnerability.
Purpose of the Study:
- To investigate the neuroprotective effects of melatonin against MPP+-induced PC12 cell death.
- To determine the influence of glucose concentration on MPP+ neurotoxicity.
Main Methods:
- PC12 cells were treated with MPP+ under varying glucose conditions (low and high).
- Cell viability was assessed using MTT assays.
- Neurotoxicity was evaluated by measuring lactate dehydrogenase (LDH) efflux and tyrosine hydroxylase (TH+) positive cell counts.
- Melatonin's neuroprotective potential was examined through pre-incubation experiments.
Main Results:
- MPP+ induced significant, time- and concentration-dependent PC12 cell death in low glucose conditions.
- High glucose levels significantly reduced MPP+-induced PC12 cell death.
- Melatonin pre-treatment markedly increased cell survival and reduced LDH leakage in MPP+-exposed cells.
- Melatonin also increased the count of tyrosine hydroxylase positive cells.
Conclusions:
- MPP+ causes concentration-dependent PC12 cell death, potentiated by low glucose and attenuated by high glucose.
- Melatonin demonstrates significant neuroprotective effects against MPP+-induced dopaminergic PC12 cell death.
- Glucose availability is a critical factor modulating neurotoxicity in this model.