title: Ghrelin protects human umbilical vein endothelial cells against high glucose-induced apoptosis via mTOR/P70S6K signaling pathway.
abstract: Ghrelin exhibits its biological effect through binding to the growth hormone secretagogue 1a receptor (GHS-R1a). Recently, it has been reported that ghrelin has an anti-apoptotic effect in several cell types. However, the molecule mechanisms underlying the anti-apoptotic effect of ghrelin remain poorly understood. In this study, we investigated the intracellular mechanisms responsible for anti-apoptotic effect of ghrelin on human umbilical vein endothelial cells (HUVEC). Treatment of HUVEC with ghrelin inhibited high glucose-induced cell apoptosis. Ghrelin stimulated the rapid phosphorylation of mammalian target of rapamycin (mTOR), P70S6K and S6. The GHS-R1a-specific antagonist [D-Lys3]-GHRP-6 abolished the anti-apoptotic effect and inhibited the activation of mTOR, P70S6K, S6 induced by ghrelin. Pretreatment of cells with specific inhibitor of mTOR blocked the anti-apoptotic effect of ghrelin. In addition, ghrelin protected HUVECs against high glucose induced apoptosis by increasing Bcl-2/Bax ratio. Taken together, our results demonstrate that ghrelin produces a protective effect on HUVECs through activating GHS-R1a and mTOR/P70S6K signaling pathway mediates the effect of ghrelin. These observations suggest that ghrelin may act as a survival factor in preventing HUVECs apoptosis caused by high glucose.
authors.affiliation: Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, PR China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, PR China; Department of Endocrinology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, PR China.
authors.forename: Chenghong
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
authors.affiliation: Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, PR China.
authors.forename: Bintao
authors.initials: B
authors.lastname: Su
authors.affiliation: Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, PR China.
authors.forename: Wen
authors.initials: W
authors.lastname: Su
authors.affiliation: Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, PR China.
authors.forename: Zixi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, PR China. Electronic address: tianpencui@hotmail.com.
authors.forename: Tianpen
authors.initials: T
authors.lastname: Cui
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D054439:Ghrelin / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D010766:Phosphorylation; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013549:Sweetening Agents / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D054439:Ghrelin; D013549:Sweetening Agents; D051028:bcl-2-Associated X Protein; C546842:MTOR protein, human; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D005947:Glucose
keywords: Apoptosis; GHS-R1a; Ghrelin; mTOR/P70S6K