Melatonin attenuates 1-methyl-4-phenylpyridinium-induced PC12 cell death
Article first published online: 13 JAN 2005
Acta Pharmacologica Sinica
Volume 26, Issue 1, pages 117–123, January 2005
How to Cite
BAO, J.-f., WU, R.-g., ZHANG, X.-p., SONG, Y. and LI, C.-l. (2005), Melatonin attenuates 1-methyl-4-phenylpyridinium-induced PC12 cell death. Acta Pharmacologica Sinica, 26: 117–123. doi: 10.1111/j.1745-7254.2005.00004.x
- Issue published online: 13 JAN 2005
- Article first published online: 13 JAN 2005
- Received 2004-06-11; Accepted 2004-08-13
- PC12 cells;
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 μmol/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+.