title: Eicosapentaenoic acid attenuates dexamethasome-induced apoptosis by inducing adaptive autophagy via GPR120 in murine bone marrow-derived mesenchymal stem cells.
abstract: Long-term use of glucocorticoids is a widespread clinical problem, which currently has no effective solution other than discontinuing the use. Eicosapentaenoic acid (EPA), an omega-3 long chain polyunsaturated fatty acid (n-3 PUFA), which is largely contained in fish or fish oil, has been reported to promote cell viability and improve bone metabolism. However, little is known about the effects of EPA on dexamethasome (Dex)-induced cell apoptosis. In this study, we showed that EPA-induced autophagy of murine bone marrow-derived mesenchymal stem cells (mBMMSCs). Meanwhile, EPA, but not arachidonic acid (AA), markedly inhibited Dex-induced apoptosis and promoted the viability of mBMMSCs. We also observed that EPA-induced autophagy was modulated by GPR120, but not GPR40. Further experiments showed that the mechanism of EPA-induced autophagy associated with GPR120 modulation involved an increase in the active form of AMP-activated protein kinase and a decrease in the activity of mammalian target of RAPA. The protective effect of EPA on Dex-induced apoptosis via GPR120-meditated induction of adaptive autophagy was supported by in vivo experiments. In summary, our findings may have important implications in developing future strategies to use EPA in the prevention and therapy of the side effects induced by long-term Dex-abuse.
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: B
authors.initials: B
authors.lastname: Gao
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Han
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital, Chengdu Medical College, Chengdu, People's Republic of China.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: W-G
authors.initials: WG
authors.lastname: Lu
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Y-Q
authors.initials: YQ
authors.lastname: Hu
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: J-Q
authors.initials: JQ
authors.lastname: Li
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: X-S
authors.initials: XS
authors.lastname: Lin
authors.affiliation: Health Science Center, Shenzhen University, 3688 Nanhai Ave, Shenzhen 518060, People's Republic of China.
authors.forename: B-H
authors.initials: BH
authors.lastname: Liu
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Q
authors.initials: Q
authors.lastname: Jie
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Z-J
authors.initials: ZJ
authors.lastname: Luo
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016718:Arachidonic Acid / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D061251:Primary Cell Culture; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C498007:FFAR4 protein, mouse; C473036:Ffar1 protein, mouse; D043562:Receptors, G-Protein-Coupled; D016718:Arachidonic Acid; D003907:Dexamethasone; D015118:Eicosapentaenoic Acid; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases