Pengjie Li1, Ying Liu1, Ying Xiang1, Miao Lin2, Jinling Gao3. 1. Department of Endocrinology, The 2nd Affiliated Hospital of Harbin Medical University Harbin 150086, China. 2. Department of Endocrinology, China General Hospital of Shenyang Military Region Shenyang 110000, China. 3. Department of Internal Medicine, Harbin Turbine Hospital Harbin 150046, China.
Abstract
OBJECTIVES: The aim of this study was to investigate the intracellular mechanism involved in the anti-apoptotic effect of ghrelin on human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were pretreated with ghrelin before exposure to 200 μg/ml advanced glycation end products (AGEs)-BSA for 48 h. Cell viability and apoptosis were determined by MTT assay and Annexin V/PI staining. Intracellular cGMP levels evaluation and cGMP analogs were employed to explore possible mechanisms. RESULTS: The inhibitory effect on AGEs induced HUVECs apoptosis could be exerted by ghrelin and co-incubation with growth hormone secretagogue receptor (GHSR)-1a antagonist [D-Lys(3)]-GHRP-6 abolished this inhibition. Decreased cGMP level in AGEs induced HUVECs apoptosis was restored by ghrelin pretreatment and abolished by [D-Lys(3)]-GHRP-6 co-incubation. cGMP analogs (8 Br-cGMP and DB-cGMP) pretreatment also exhibited inhibitory effect on AGEs induced HUVECs apoptosis. CONCLUSIONS: Our results demonstrated that ghrelin produces a protective effect on HUVECs through GHS-R1a and cGMP/NO signaling pathway mediates the effect of ghrelin. These observations suggest a novel intracellular mechanism in the process of AGEs induced HUVECs apoptosis.
OBJECTIVES: The aim of this study was to investigate the intracellular mechanism involved in the anti-apoptotic effect of ghrelin on human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were pretreated with ghrelin before exposure to 200 μg/ml advanced glycation end products (AGEs)-BSA for 48 h. Cell viability and apoptosis were determined by MTT assay and Annexin V/PI staining. Intracellular cGMP levels evaluation and cGMP analogs were employed to explore possible mechanisms. RESULTS: The inhibitory effect on AGEs induced HUVECs apoptosis could be exerted by ghrelin and co-incubation with growth hormone secretagogue receptor (GHSR)-1a antagonist [D-Lys(3)]-GHRP-6 abolished this inhibition. Decreased cGMP level in AGEs induced HUVECs apoptosis was restored by ghrelin pretreatment and abolished by [D-Lys(3)]-GHRP-6 co-incubation. cGMP analogs (8 Br-cGMP and DB-cGMP) pretreatment also exhibited inhibitory effect on AGEs induced HUVECs apoptosis. CONCLUSIONS: Our results demonstrated that ghrelin produces a protective effect on HUVECs through GHS-R1a and cGMP/NO signaling pathway mediates the effect of ghrelin. These observations suggest a novel intracellular mechanism in the process of AGEs induced HUVECs apoptosis.
Authors: P J D Delhanty; B C J van der Eerden; M van der Velde; C Gauna; H A P Pols; H Jahr; H Chiba; A J van der Lely; J P T M van Leeuwen Journal: J Endocrinol Date: 2006-01 Impact factor: 4.286
Authors: R Peino; R Baldelli; J Rodriguez-Garcia; S Rodriguez-Segade; M Kojima; K Kangawa; E Arvat; E Ghigo; C Dieguez; F F Casanueva Journal: Eur J Endocrinol Date: 2000-12 Impact factor: 6.664