title: Cytoprotective effects of melatonin on astroglial cells subjected to palmitic acid treatment in vitro.
abstract: Melatonin, an endogenously produced neurohormone secreted mainly by the pineal gland, has a variety of physiological functions and neuroprotective effects. Saturated fatty acids (SFAs) have been known to induce neurotoxicity and oxidative stress in central nervous system injuries and neurodegenerative pathologies. However, the effect of melatonin on SFAs-induced cytotoxicity in astroglial cells, if any, has remained to be explored. This study reports that in primary cultured astroglial cells, melatonin significantly attenuated palmitic acid (PA)-induced cytotoxicity in a concentration- and time-dependent manner. Additionally, melatonin effectively suppressed PA-induced reactive oxygen species generation and prevented PA-induced apoptosis whereby the rise in Bax/Bcl-2 ratio and caspase-3 activation in astroglial cells was inhibited. However, it did not appear to exert an obvious effect on PA-induced intracellular calcium overload. Luzindole, a nonselective melatonin receptor antagonist, attenuated melatonin's promotion effect of cell survival and Stat3 phosphorylation, indicating that melatonin exerts its protective property in astroglial cells, at least in part, through the activation of membrane receptors and then Stat3 signaling pathway. Finally, melatonin had an inhibitory effect on the pro-inflammatory cytokine gene expression. The results suggest that melatonin may be an effective cytoprotective agent against PA-based cytotoxicity through modulating cell survival and inflammatory response in astroglial cells.
authors.affiliation: Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Dexiang
authors.initials: D
authors.lastname: Liu
authors.forename: Juntao
authors.initials: J
authors.lastname: Wang
authors.forename: Shangming
authors.initials: S
authors.lastname: Liu
authors.forename: Ming
authors.initials: M
authors.lastname: Gao
authors.forename: Eng-Ang
authors.initials: EA
authors.lastname: Ling
authors.forename: Aijun
authors.initials: A
authors.lastname: Hao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D019610:Cytoprotection / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000633:toxicity; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019308:Palmitic Acid / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D019308:Palmitic Acid; D008550:Melatonin