Ghrelin protects human umbilical vein endothelial cells against high glucose-induced apoptosis via mTOR/P70S6K signaling pathway |
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| Affiliation: | 1. Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, PR China;2. Department of Endocrinology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, PR China;3. Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, PR China;1. Natural Drug Discovery Group, School of Pharmacy, Queen''s University, Belfast BT9 7BL, Northern Ireland, UK;2. School of Medicine, Shenzhen University, PR China;3. Division of Molecular Cardiology, Department of Internal Medicine, College of Medicine, Texas A&M University Health Science Center, Central Texas Veterans Health Care System, Temple, TX 76504, USA;1. Institute of Cardiovascular Disease Research, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, Jiangsu 221002, China;2. Department of Cardiology, The Affiliated Hospital of Xuzhou Medical College, 99 West Huaihai Road, Xuzhou, Jiangsu 221002, China;1. Department of Physiology, E. Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation, Novosibirsk, Russia;2. Department of Cardiac Surgery, E. Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation, Novosibirsk, Russia;3. Department of Anesthesia and Intensive Care, E. Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation, Novosibirsk, Russia;4. E. Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation, Novosibirsk, Russia;1. Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain;2. Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain;3. Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain;1. Division of Cardiovascular Surgery, University of Pennsylvania, Philadelphia, Pennsylvania;1. Departamento de Cirurgia e Fisiologia, Unidade de Investigação Cardiovascular, Faculdade de Medicina da Universidade do Porto, Porto, Portugal;2. Serviço de Angiologia e Cirurgia Vascular, Centro Hospitalar São João, Porto, Portugal;3. Centro de Investigação e Tecnologia de Informação em Sistemas de Saúde (CINTESIS) e Departamento de Ciências da Informação e da Decisão em Saúde, Faculdade de Medicina da Universidade do Porto, Porto, Portugal;4. Serviço de Angiologia e Cirurgia Vascular, Centro Hospitalar Tãmega e Sousa, Penafiel, Portugal;5. Serviço de Angiologia e Cirurgia Vascular, Centro Hospitalar Lisboa Norte, Centro Hospitalar Lisboa Central, Lisboa, Portugal;6. Serviço de Angiologia e Cirurgia Vascular, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal;7. Serviço de Angiologia e Cirurgia Vascular, Centro Hospitalar Lisboa Central, Lisboa, Portugal;8. Serviço de Angiologia e Cirurgia Vascular, Centro Hospitalar de Vila Nova de Gaia e Espinho, Espinho, Portugal |
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| 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. |
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| Keywords: | Ghrelin Apoptosis mTOR/P70S6K GHS-R1a |
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