title: L-arginine attenuates high glucose-accelerated senescence in human umbilical vein endothelial cells.
abstract: OBJECTIVE
  Endothelial dysfunction is a key event in the onset and progression of atherosclerosis associated with diabetes. Increasing cell senescence may lead to endothelial dysfunction and contribute to vascular complications. Therefore, we aimed to elucidate the possible role and mechanism of L-arginine in preventing cell senescence induced by high glucose.
  
  
  METHODS
  HUVECs were respectively cultured under normal control glucose (5.5mM), high glucose (33mM), co-incubation with L-arginine (800microM)and high glucose, and senescence was identified by beta-galactosidase staining, change of cell cycle and telomerase activity. Akt and eNOS activity was analyzed by western blot.
  
  
  RESULTS
  High glucose significantly increased number of beta-galactosidase-positive stained cells, inhibited telomerase activity, increased proportion of cells in the G(0)/G(1) phase and reduced proportion in the S phase, and decreased NO synthesis. L-arginine significantly attenuated these senescent alterations. Furthermore, high glucose induced a decrease in Akt and eNOS activity, and L-arginine prevented the decrease in activity. The PI3K inhibitor LY294002 or eNOS inhibitor L-NAME attenuated anti-senescence effect of L-arginine.
  
  
  CONCLUSIONS
  L-arginine may have an anti-senescence effect via the PI3K/Akt pathway in HUVECs exposed to high glucose and it might be a therapeutic agent for diabetic vascular complications.
authors.affiliation: Department of Endocrinology, First Affiliated Hospital of China Medical University, Shen Yang, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Zhong
authors.forename: Guoliang
authors.initials: G
authors.lastname: Zou
authors.forename: Jianqiu
authors.initials: J
authors.lastname: Gu
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
mesh_terms: D001120:Arginine / Q000494:pharmacology*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects; D005947:Glucose / Q000633:toxicity*; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D016196:S Phase / Q000187:drug effects; D019098:Telomerase / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D009569:Nitric Oxide; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D001120:Arginine; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019098:Telomerase; D001616:beta-Galactosidase; D005947:Glucose; D019331:NG-Nitroarginine Methyl Ester