title: Ghrelin inhibits apoptosis induced by high glucose and sodium palmitate in adult rat cardiomyocytes through the PI3K-Akt signaling pathway.
abstract: OBJECTIVE
  Ghrelin is a gastric acyl-peptide that has been identified as an endogenous ligand for the growth hormone secretagogue receptor. It has been reported to have cardioprotective activities independent of growth hormone release. We investigated the effect of ghrelin on apoptosis induced by high glucose and sodium palmitate and the mechanisms underlying the cardioprotective activities of ghrelin.
  
  
  METHODS
  Cardiomyocytes were isolated from hearts of adult rats and cultured in serum-free MEM. High glucose (30 mM) or sodium palmitate (0.5 mM) were used to induce apoptosis. Apoptosis was detected using an annexin V-FITC/PI binding assay and a caspase 3 activity assay. Reactive oxygen species were detected using a DCFH-DA fluorescent probe. Phospho-Akt, phospho-ERK, and NF kappaB levels were determined using ELISA. The transcription of genes was analyzed using real-time PCR.
  
  
  RESULTS
  Ghrelin can inhibit apoptosis induced by oxidative stress in cardiomyocytes from adult rats through the activation of the PI3K-Akt signaling pathway. In addition, ghrelin does not decrease intracellular oxidative stress. Activation of the MEK-ERK1/2 signaling pathway has no influence on the inhibition of apoptosis. Finally, ghrelin activates NF kappaB and subsequently increases the transcription of survival genes such as Bcl-2, Bcl-xL, c-iap, and c-fos.
  
  
  CONCLUSIONS
  Our research provides evidence that ghrelin may act as a survival factor under oxidative stress in cardiomyocytes. This may provide a clue for therapy for myocardial disease in diabetes mellitus.
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Kui
authors.forename: Zhang
authors.initials: Z
authors.lastname: Weiwei
authors.forename: Liu
authors.initials: L
authors.lastname: Ling
authors.forename: He
authors.initials: H
authors.lastname: Daikun
authors.forename: Zhou
authors.initials: Z
authors.lastname: Guoming
authors.forename: Zhou
authors.initials: Z
authors.lastname: Linuo
authors.forename: Hu
authors.initials: H
authors.lastname: Renming
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D054439:Ghrelin / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D019308:Palmitic Acid / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013549:Sweetening Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D054439:Ghrelin; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D013549:Sweetening Agents; D019308:Palmitic Acid; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D005947:Glucose