title: TRAIL protects against endothelium injury in diabetes via Akt-eNOS signaling.
abstract: OBJECTIVE
  Although some studies have suggested that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) might be involved in atherosclerosis, its potential role in endothelial dysfunction and apoptosis has not been investigated. The aim of this study was to evaluate the impact of TRAIL on endothelium injury in diabetes and the underlying mechanism involved.
  
  
  METHODS
  Experimental diabetes was induced using streptozotocin in rats. Cohorts of diabetic rats received an intraperitoneal injection of recombinant TRAIL (rTRAIL) 20 μg per rat weekly for 6 weeks. Endothelial function was assessed by acetylcholine (Ach)-induced endothelium-dependent vasorelaxation using aortic rings. The antiapoptotic effects of TRAIL and its possible mechanisms were investigated in cultured human umbilical vein endothelial cells (HUVECs).
  
  
  RESULTS
  Experimental diabetes attenuated endothelial function, which was significantly improved by rTRAIL treatment (63.5 ± 4.62% vs. 78.4 ± 2.79%, P < 0.01). In cultured HUVECs, TRAIL suppressed high glucose-induced reactive oxygen species (ROS) production and cellular apoptosis, as well as the production of NADPH oxidase. Furthermore, the antiapoptotic actions of TRAIL were accompanied by Akt and endothelial nitric oxide synthase (eNOS) phosphorylation, as well as increased NO production.
  
  
  CONCLUSIONS
  These findings indicate a novel role of TRAIL in the protection against vascular injury in diabetes. The protective effects of TRAIL are dependent on the activation of Akt-dependent eNOS signaling.
authors.affiliation: Department of Endocrinology, Wuhan General Hospital of Guangzhou Command, Wuluo Road 627, Wuhan 430070, Hubei Province, China. Electronic address: laojunyi3@126.com.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Wuhan General Hospital of Guangzhou Command, Wuluo Road 627, Wuhan 430070, Hubei Province, China. Electronic address: Guangda64@hotmail.com.
authors.forename: Guangda
authors.initials: G
authors.lastname: Xiang
authors.affiliation: Department of Endocrinology, Wuhan General Hospital of Guangzhou Command, Wuluo Road 627, Wuhan 430070, Hubei Province, China. Electronic address: buyuelingyun@outlook.com.
authors.forename: Junyan
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Endocrinology, Wuhan General Hospital of Guangzhou Command, Wuluo Road 627, Wuhan 430070, Hubei Province, China. Electronic address: xianglin832010@hotmail.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Xiang
authors.affiliation: Department of Endocrinology, Wuhan General Hospital of Guangzhou Command, Wuluo Road 627, Wuhan 430070, Hubei Province, China. Electronic address: 36474533@qq.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Endocrinology, Wuhan General Hospital of Guangzhou Command, Wuluo Road 627, Wuhan 430070, Hubei Province, China. Electronic address: xiaomeiwen@outlook.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Mei
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000473:pathology*; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008297:Male; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D053221:TNF-Related Apoptosis-Inducing Ligand; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C402799:NOX1 protein, human; D019869:Phosphatidylinositol 3-Kinases; C494918:AKT1 protein, human; C494920:Akt1 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose
keywords: Diabetes; Endothelium; Oxidative stress; PI3K/Akt; Tumor necrosis factor-related apoptosis-inducing ligand