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Cytoprotective effects of melatonin on C6 astroglial cells exposed to glutamate excitotoxicity and oxidative stress
Author(s) -
Das Arabinda,
Belagodu Amogh,
Reiter Russel J.,
Ray Swapan K.,
Banik Naren L.
Publication year - 2008
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.2008.00582.x
Subject(s) - melatonin , excitotoxicity , oxidative stress , apoptosis , glutamate receptor , spectrin , biology , programmed cell death , western blot , free radical scavenger , pharmacology , microbiology and biotechnology , endocrinology , chemistry , medicine , biochemistry , cell , receptor , cytoskeleton , gene
To preserve the central nervous system (CNS) function after a traumatic injury, therapeutic agents must be administered to protect neurons as well as glial cells. Cell death in CNS injuries and diseases are attributed to many factors including glutamate toxicity and oxidative stress. We examined whether melatonin, a potent anti‐oxidant and free radical scavenger, would attenuate apoptotic death of rat C6 astroglial cells under glutamate excitotoxicity and oxidative stress. Exposure of C6 cells to 500 μ m l ‐glutamic acid (LGA) and 100 μ m hydrogen peroxide (H 2 O 2 ) for 24 hr caused significant increases in apoptosis. Apoptosis was evaluated by Wright staining and ApopTag assay. Melatonin receptor 1 appeared to be involved in the protection of these cells from excitotoxic and oxidative damage. Cells undergoing excitotoxic and oxidative stress for 15 min were then treated with 150 n m melatonin, which prevented Ca 2+ influx and cell death. Western blot analyses showed alterations in Bax and Bcl‐2 expression resulting in increased Bax:Bcl‐2 ratio during apoptosis. Western blot analyses also showed increases in calpain and caspase‐3 activities, which cleaved 270 kD α‐spectrin at specific sites to generate 145 kD spectrin breakdown product (SBDP) and 120 kD SBDP, respectively. However, 15‐min post‐treatment of C6 cells with melatonin dramatically reduced Bax:Bcl‐2 ratio and proteolytic activities, decreasing LGA or H 2 O 2 ‐induced apoptosis. Our data showed that melatonin prevented proteolysis and apoptosis in C6 astroglial cells. The results suggest that melatonin may be an effective cytoprotective agent against glutamate excitotoxicity and oxidative stress in CNS injuries and diseases.