title: Early inactivation of PKCε associates with late mitochondrial translocation of Bad and apoptosis in ventricle of septic rat.
abstract: BACKGROUND
  Sepsis is usually accompanied by cardiomyocyte apoptosis and myocardial depression. Protein kinase C (PKC) has been reported to be important in regulating cardiac function and apoptosis; however, which PKC isoform is involved in sepsis-induced myocardial apoptosis remains unknown.
  
  
  METHODS
  A rat model of sepsis by cecal ligation and puncture was used. Early and late sepsis refers to those rats sacrificed at 9 and 18 h after cecal ligation and puncture, respectively. Ventricular septum (Sep), left ventricle (LV), and right ventricle were fractionated into membrane, mitochondrial, and cytosolic fractions, individually. The protein levels of PKC isoforms (-α, -β, -δ, -ε, -ζ, -ι, -λ, and -μ) and mitochondrial translocation of Bad were quantified by Western blot analysis. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP in situ nick-end labeling. The morphology of mitochondria was examined by electron microscopy.
  
  
  RESULTS
  The membrane/cytosol ratio of PKCε was predominantly higher in the Sep, LV, and right ventricle under physiological conditions. At early sepsis, the membrane/cytosol ratio of PKCε was significantly decreased in Sep and LV. At late sepsis, cardiomyocyte apoptosis associated with severe mitochondrial swelling and crista derangement were observed in Sep and LV at late sepsis. Additionally, mitochondria/cytosol ratio of Bad was significantly increased in Sep and LV.
  
  
  CONCLUSIONS
  The early inactivation of PKCε in the ventricle may affect the mitochondrial translocation of Bad and subsequent mitochondrial disruption and apoptosis at late sepsis. This finding opens up the prospect for a potential therapeutic strategy targeting PKCε activation to prevent myocardial depression in septic patients.
authors.affiliation: Department of Physiology, School of Medicine, Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ke-Li
authors.initials: KL
authors.lastname: Tsai
authors.forename: Hsin-Jen
authors.initials: HJ
authors.lastname: Liang
authors.forename: Zheng-Dao
authors.initials: ZD
authors.lastname: Yang
authors.forename: Sheng-I
authors.initials: SI
authors.lastname: Lue
authors.forename: Shaw-Lang
authors.initials: SL
authors.lastname: Yang
authors.forename: Chin
authors.initials: C
authors.lastname: Hsu
mesh_terms: D000818:Animals; D017209:Apoptosis; D006352:Heart Ventricles; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000502:physiology*; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000378:metabolism* / Q000473:pathology; D051025:bcl-Associated Death Protein / Q000378:metabolism*
chemical_list: C494821:Bad protein, rat; D051025:bcl-Associated Death Protein; C497257:Prkce protein, rat; D051744:Protein Kinase C-epsilon
keywords: Bad; Cardiomyocyte apoptosis; Mitochondria; PKCε; Sepsis