title: [The protective effects of insulin on cardiocyte apoptosis challenged by burn serum].
abstract: OBJECTIVE
  To investigate the protective effects of insulin on burn serum-challenged cardiocyte apoptosis and its mechanism.
  
  
  METHODS
  Burn-serum challenged cardiocytes were pretreated with insulin and inhibitors to pathway SB203580 and LY294002. The expression of cardiac myofilament proteins cleaved-caspase-3, Bax and phosphorylation nuclear factor-ΚB inhibitive factor α (p-IΚBα) were examined by Western blotting. The mRNA expression of tumor necrosis factor-α (TNF-α) was determined by real-time reverse transcription-polymerase chain reaction (RT-PCR). Apoptosis of cardiocyte was observed after Hoechst 33258 staining. Further blocking experiments were used to investigate the cytoprotective pathway of insulin.
  
  
  RESULTS
  Insulin could significantly decrease the expression of cleaved-caspase-3 (2.22 ± 0.30  vs.  4.84 ± 0.74, P < 0.01), Bax (1.33 ± 0.35  vs.  3.74 ± 0.65, P < 0.01), p-IΚBα (1.43 ± 0.62  vs.  3.62 ± 0.74, P < 0.01), TNF-α (0.72 ± 0.27  vs.  2.02 ± 0.63, P < 0.01) and the cardiocyte apoptosis rate [(9.4 ± 3.4)%  vs.  (19.1 ± 5.6)%, P < 0.01] in cardiocytes challenged by burn serum. Further blocking experiments showed that LY294002, phosphatidylinositol-3-kinase (PI3K)/Akt activation inhibitor, could mitigate the protective effects of insulin. Meanwhile, SB203580, an inhibitor of p38 mitogen-activated protein kinase (p38MAPK) pathway, was able to inhibit cardiocyte injury challenged by burn serum, and it was as effective as insulin.
  
  
  CONCLUSIONS
  For cardiocytes challenged by burn serum, insulin may decrease inflammatory cytokine expression and apoptosis via regulating PI3K/Akt and p38MAPK pathway.
authors.affiliation: Department of Burns and Plastic Surgery, the 534th Hospital of PLA, Luoyang 471003, Henan, China. genfalu@yahoo.com.cn
authors.forename: Gen-Fa
authors.initials: GF
authors.lastname: Lü
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Shi
authors.forename: Guang-yuan
authors.initials: GY
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Fan
authors.forename: Da-hai
authors.initials: DH
authors.lastname: Hu
authors.forename: Bi
authors.initials: B
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002056:Burns / Q000097:blood; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011725:Pyridines / Q000494:pharmacology; D044967:Serum / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D002867:Chromones; D007093:Imidazoles; D007328:Insulin; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580