title: Ghrelin protects human umbilical vein endothelial cells against advanced glycation end products-induced apoptosis via NO/cGMP signaling.
abstract: OBJECTIVE
  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.affiliation: Department of Endocrinology, The 2nd Affiliated Hospital of Harbin Medical University Harbin 150086, China.
authors.forename: Pengjie
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Endocrinology, The 2nd Affiliated Hospital of Harbin Medical University Harbin 150086, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, The 2nd Affiliated Hospital of Harbin Medical University Harbin 150086, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Department of Endocrinology, China General Hospital of Shenyang Military Region Shenyang 110000, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine, Harbin Turbine Hospital Harbin 150046, China.
authors.forename: Jinling
authors.initials: J
authors.lastname: Gao
keywords: GHS-R1a; Ghrelin; HUVECs; apoptosis; cGMP/NO signaling