Docosahexaenoic acid alters Gs[alpha] localization in lipid raft and potentiates adenylate cyclase

• Published in: Nutrition (Burbank, Los Angeles County, Calif.) Los Angeles County, Calif.), 2015-07, Vol.31 (7-8), p.1025
• Main Authors: Zhu, Zhuoran, Tan, Zhoubin, Li, Yan, Luo, Hongyan, Hu, Xinwu, Tang, Ming, Hescheler, Jürgen, Mu, Yangling, Zhang, Lanqiu
• Format: Article
• Language: English
• Subjects: Antidepressants; Cholesterol; Hypotheses; Lipids; Mental depression; Microscopic analysis; Neurogenesis; Polyunsaturated fatty acids; Proteins; Studies; Substance abuse treatment; Sucrose; Suicides & suicide attempts
• ISSN: 0899-9007; 1873-1244
• DOI: 10.1016/j.nut.2015.02.012

Objective Supplementation with docosahexaenoic acid (DHA), an [omega]-3 polyunsaturated fatty acid (PUFA), recently has become popular for the amelioration of depression; however the molecular mechanism of DHA action remains unclear. The aim of this study was to investigate the mechanism underlying the antidepressant effect of DHA by evaluating Gs[alpha] localization in lipid raft and the activity of adenylate cyclase in an in vitro glioma cell model. Methods Lipid raft fractions from C6 glioma cells treated chronically with DHA were isolated by sucrose gradient ultracentrifugation. The content of Gs[alpha] in lipid raft was analyzed by immunoblotting and colocalization of Gs[alpha] with lipid raft was subjected to confocal microscopic analysis. The intracellular cyclic adenosine monophosphate (cAMP) level was determined by cAMP immunoassay kit. Results DHA decreased the amount of Gs[alpha] in lipid raft, whereas whole cell lysate Gs[alpha] was not changed. Confocal microscopic analysis demonstrated that colocalization of Gs[alpha] with lipid raft was decreased, whereas DHA increased intracellular cAMP accumulation in a dose-dependent manner. Interestingly, we found that DHA increased the lipid raft level, instead of disrupting it. Conclusions The results of this study suggest that DHA may exert its antidepressant effect by translocating Gs[alpha] from lipid raft and potentiating the activity of adenylate cyclase. Importantly, the reduced Gs[alpha] in lipid raft by DHA is independent of disruption of lipid raft. Overall, the study provides partial preclinical evidence supporting a safe and effective therapy using DHA for depression.