title: [Association between myocardial calpain activation and apoptosis in lipopolysaccharide-induced septic mouse model].
abstract: OBJECTIVE
  in septic mice, myocardial calpain was activated and induced caspase-3 activation, the association between calpain activation and apoptosis was explored in this experiment.
  
  
  METHODS
  in in vivo model, adult C57 mice were injected with lipopolysaccharide (LPS, 4 mg/kg, i.p.) to induce sepsis. Myocardial calpain and caspase-3 activities, protein levels of calpain-1, calpain-2, calpastatin, Bcl-2 and Bid were detected by Western blot analysis and myocardial apoptosis was detected by TUNEL, myocardiac function was evaluated by Langendorff system. In in vitro model, adult rat cardiomyocytes were incubated with LPS (1 microg/ml) or co-incubated with calpain inhibitor-III (10 micromol/L), calpain activity, caspase-3 activity, protein levels of Bcl-2 and Bid, and cardiomyocyte apoptosis were detected.
  
  
  RESULTS
  in septic mice, myocardial calpain and caspase-3 activity were increased up to 2.7- and 1.8-folds, respectively. Both calpain inhibitor-III and PD150606 significantly attenuated the increase of caspase-3 activity. Myocardial protein levels of calpain-1, calpain-2, calpastatin, Bcl-2 and Bid were similar between control and septic mice, and no cleavage of both Bcl-2 and Bid was found in septic mice. Calpain inhibitor-III significantly improved myocardial function in septic mice. In in vitro model, calpain and caspase-3 activities were increased after 4 h LPS treatment, co-treatment with calpain inhibitor-III prevented caspase-3 activity increase, protein Bcl-2 and Bid were similar between normal cardiomyocytes and LPS-treated cardiomyocytes. Cardiomyocyte apoptosis was similar in in vivo and in vitro septic models.
  
  
  CONCLUSIONS
  myocardial calpain activity is increased in LPS induced septic mice, subsequent caspase-3 activation may contribute to myocardial dysfunction in septic mice without aggravating myocardial apoptosis and Bcl-2 and Bid are not involved on calpain induced caspase-3 activation in our model.
authors.affiliation: Key Laboratory of Viral Heart Disease, Ministry of Public Health, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Xiao-ping
authors.initials: XP
authors.lastname: LI
authors.forename: Lang
authors.initials: L
authors.lastname: LI
authors.forename: Rui-zhen
authors.initials: RZ
authors.lastname: CHEN
authors.forename: Tang-wei
authors.initials: TW
authors.lastname: LIU
authors.forename: Wei-feng
authors.initials: WF
authors.lastname: WU
authors.forename: E
authors.initials: E
authors.lastname: SHEN
authors.forename: Ying-zhen
authors.initials: YZ
authors.lastname: YANG
authors.forename: Hao-zhu
authors.initials: HZ
authors.lastname: CHEN
mesh_terms: D000818:Animals; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D018805:Sepsis / Q000378:metabolism*
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; C494815:Bid protein, mouse; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C410340:calpain activator; C052617:Bcl2 protein, mouse; D002154:Calpain; C505409:Casp3 protein, mouse; D053148:Caspase 3; D002118:Calcium