title: Docosahexaenoic acid alters Gsα localization in lipid raft and potentiates adenylate cyclase.
abstract: OBJECTIVE
  Supplementation with docosahexaenoic acid (DHA), an ω-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 Gsα 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 Gsα in lipid raft was analyzed by immunoblotting and colocalization of Gsα 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 Gsα in lipid raft, whereas whole cell lysate Gsα was not changed. Confocal microscopic analysis demonstrated that colocalization of Gsα 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 Gsα from lipid raft and potentiating the activity of adenylate cyclase. Importantly, the reduced Gsα 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.
authors.affiliation: Department of Physiology, Chinese-German Stem Cell Center, Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Hubei Province, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China; The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhuoran
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Physiology, Chinese-German Stem Cell Center, Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Hubei Province, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhoubin
authors.initials: Z
authors.lastname: Tan
authors.affiliation: Department of Physiology, Chinese-German Stem Cell Center, Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Hubei Province, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China; The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Physiology, Chinese-German Stem Cell Center, Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Hubei Province, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China; The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Physiology, Chinese-German Stem Cell Center, Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Hubei Province, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China; The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xinwu
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Physiology, Chinese-German Stem Cell Center, Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Hubei Province, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China; The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Tang
authors.affiliation: Institute for Neurophysiology, University of Cologne, Cologne, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hescheler
authors.affiliation: Department of Physiology, Chinese-German Stem Cell Center, Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Hubei Province, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China; The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yangling
authors.initials: Y
authors.lastname: Mu
authors.affiliation: Department of Physiology, Chinese-German Stem Cell Center, Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Hubei Province, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China; The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China; Tianjin Nankai Hospital, Tianjin, China. Electronic address: Lanqiuzhang@126.com.
authors.forename: Lanqiu
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000032:analysis; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D021962:Membrane Microdomains / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000928:Antidepressive Agents; D004281:Docosahexaenoic Acids; D000242:Cyclic AMP; D019205:GTP-Binding Protein alpha Subunits, Gs; D000262:Adenylyl Cyclases
keywords: Adenylate cyclase; Antidepressant; Docosahexaenoic acid; Gsα; Lipid raft