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Melatonin prevents apoptosis induced by 6‐hydroxydopamine in neuronal cells: Implications for Parkinson's disease
Author(s) -
Mayo Juan Carlos,
Sainz Rosa Maria,
Uria Higinio,
Antolin Isaac,
Esteban Manuel M.,
Rodriguez Carmen
Publication year - 1998
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.1998.tb00531.x
Subject(s) - melatonin , hydroxydopamine , apoptosis , programmed cell death , neurotoxin , endogeny , dna fragmentation , biology , free radical scavenger , viability assay , microbiology and biotechnology , parkinson's disease , antioxidant , medicine , endocrinology , biochemistry , disease
It was recently reported that low doses of 6‐hydroxydopamine (6‐OHDA) induce apoptosis of naive (undifferentiated) and neuronal (differentiated) PC 12 cells, and this system has been proposed as an adequate experimental model for the study of Parkinson's disease. The mechanism by which this neurotoxin damages cells is via the production of free radicals. Given that the neurohormone melatonin has been reported 1) to be a highly effective endogenous free radical scavenger, 2) to increase the mRNA levels and the activity of several antioxidant enzymes, and 3) to inhibit apoptosis in other tissues, we have studied the ability of melatonin to prevent the programmed cell death induced by 6‐OHDA in PC12 cells. We found that melatonin prevents the apoptosis caused by 6‐OHDA in naive and neuronal PC12 cells as estimated by 1) cell viability assays, 2) counting of the number of apoptotic cells, and 3) analysis and quantification of DNA fragmentation. Exploration of the mechanisms used by melatonin to reduce programmed cell death revealed that this chemical mediator prevents the 6‐OHDA induced reduction of mRNAs for several antioxidant enzymes. The possibility that melatonin utilized additional mechanisms to prevent apoptosis of these cells is also discussed. Since this endogenous agent has no known side effects and readily crosses the blood‐brain‐barrier, we consider melatonin to have a high clinical potential in the treatment of Parkinson's disease and possibly other neurodegenerative diseases, although more research on the mechanisms is yet to be done.