title: Protein kinase C isoforms responsible for the regulation of vascular calcium sensitivity and their relationship to integrin-linked kinase pathway after hemorrhagic shock.
abstract: BACKGROUND
  The aim of this study was to investigate the protein kinase C (PKC) isoforms involved in the regulation of vascular calcium sensitivity after hemorrhagic shock, the related mechanism, and the role of integrin-linked kinase (ILK).
  
  
  METHODS
  Using superior mesenteric artery from hemorrhagic shock rats and hypoxia-treated vascular smooth muscle cells, the effects of PKC isoforms agonists and antagonists on vascular calcium sensitivity, their relationship with myosin light chain phosphatase (MLCP), myosin light chain (MLC20) phosphorylation, and ILK were observed.
  
  
  RESULTS
  The results indicated that PKCα and ε agonists, thymelea toxin and carbachol, restored shock-induced decrease of vascular calcium sensitivity; PKCα antagonist, Gö-6976 and PKCε pseudosubstrate inhibition peptide, aggravated shock-induced calcium desensitization, whereas the agonists and antagonists of PKCδ and ζ had no effects on shock-induced calcium desensitization. PKCα and ε agonists reversed the increased MLCP activity and the decreased MLC20 phosphorylation induced by shock or hypoxia. ILK inhibitor abolished the effects of PKCα and ε agonists on vascular calcium sensitivity, MLCP activity, and MLC20 phosphorylation.
  
  
  CONCLUSIONS
  These findings suggested that PKCα and ε may be the main isoforms responsible for the regulation of vascular calcium sensitivity after hemorrhagic shock, which enforce their regulation through MLCP-MLC20 pathway, and ILK may be a downstream molecule of PKCα and ε.
authors.affiliation: State Key Laboratory of Trauma, Burns, and Combined Injury, The 2nd Department of Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Guang-Ming
authors.initials: GM
authors.lastname: Yang
authors.forename: Liang-Ming
authors.initials: LM
authors.lastname: Liu
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D020033:Protein Isoforms / Q000494:pharmacology; D011493:Protein Kinase C / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D017208:Rats, Wistar; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects*; D000099200:Scaffold Protein ILK
chemical_list: D002118:Calcium; D002227:Carbazoles; D004791:Enzyme Inhibitors; D020033:Protein Isoforms; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK; C081021:Go 6976