title: TNF-α- mediated-p38-dependent signaling pathway contributes to myocyte apoptosis in rats subjected to surgical trauma.
abstract: BACKGROUND
  The accumulation of cytokines in the plasma after trauma can induce myocyte apoptosis. We aimed to identify which cytokine(s) present in the plasma responsible for myocyte apoptosis, and delineated the signal transduction mechanism in rats subjected to surgical trauma.
  
  
  METHODS
  Rats were randomized into two groups: control and trauma groups, which was divided into five subgroups: posttraumatic 0, 3, 6, 12, and 24 h subgroups. Cardiomyocytes isolated from traumatized rats were incubated with one of the factors for 12 h (normal plasma; Cytomix; TNF-α; IL-1β; IFN-γ; trauma plasma; anti-TNF-α antibody; SB203580). Myocyte apoptosis, cytokine levels, and MAPKs activation, as the primary experimental outcomes, were measured by TUNEL, flow cytometry, ELISA and Western blot, respectively.
  
  
  RESULTS
  Myocyte apoptosis was induced by surgical trauma during the early stage after trauma. Accompanying this change, plasma TNF-α, IL-1β, and IFN-γ levels were elevated in traumatized rats. Incubation of traumatized cardiomyocytes with cytomix or TNF-α alone induced myocyte apoptosis, and increased the activation of p38 and ERK1/2. Myocyte apoptosis and p38 activation were elevated in traumatized cardiomyocytes with trauma plasma, and these increases were partly abolished by anti-TNF-α antibody or SB203580.
  
  
  CONCLUSIONS
  Our study demonstrated that there exists the TNF-α-mediated-p38-dependent signaling pathway that contributed to posttraumatic myocyte apoptosis of rats undergoing surgical trauma.
authors: School of Life science and technology, Harbin Institute of Technology, Harbin, China.
authors: Huaxing
authors: H
authors: Wu
authors: Guonian
authors: G
authors: Wang
authors: Shuai
authors: S
authors: Li
authors: Mingyue
authors: M
authors: Zhang
authors: Hulun
authors: H
authors: Li
authors: Kun
authors: K
authors: Wang
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology / Q000494:pharmacology*; D014947:Wounds and Injuries / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000906:Antibodies; D016207:Cytokines; D007093:Imidazoles; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases; C093642:SB 203580