title: Role of non-MLC20 phosphorylation pathway in the regulation of vascular reactivity during shock.
abstract: BACKGROUND
  Studies have shown that shock-induced vascular hyporeactivity is associated with the decrease in 20-kDa myosin light chain (MLC20) phosphorylation. Whether and how a non-MLC20 phosphorylation pathway participates in the regulation of vascular reactivity after shock is not known.
  
  
  METHODS
  With superior mesentery artery (SMA) obtained from rats in hemorrhagic shock and hypoxia-treated SMA, the regulatory effect of platelet-derived growth factor (PDGF) on vascular reactivity and the roles of caldesmon, 27-kDa heat shock protein (HSP27), extracellular signal-regulated protein kinase (Erk), and p38 mitogen-activated protein kinase (MAPK), the main molecules that are involved in the non-MLC20 phosphorylation pathway of the regulation of smooth-muscle contraction, were investigated.
  
  
  RESULTS
  PDGF (40-100 ng/mL) increased the vascular reactivity after shock in a dose-dependent manner, whereas it did not increase the MLC20 phosphorylation in a dose-dependent manner. PDGF with concentration more than 60 ng/mL did not further increase the MLC20 phosphorylation, whereas upregulated the phosphorylation of HSP27, Erk, and p38MAPK, and the activity of myosin adenosine triphosphatase in SMAs, and downregulated the phosphorylation of caldesmon. p38MAPK antagonist, SB203580, not only antagonized PDGF-induced increase in the phosphorylation of HSP27, but also antagonized PDGF-induced decrease in the phosphorylation of caldesmon, whereas Erk antagonist, PD98059, only antagonized PDGF-induced decrease in the phosphorylation of caldesmon.
  
  
  CONCLUSIONS
  These findings suggested that a non-MLC20 phosphorylation pathway participated in the regulation of vascular reactivity after shock. Caldesmon- and HSP27-mediated change in myosin adenosine triphosphatase activity and Erk and p38MAPK played an important role in this process. These findings may provide some potential targets for the treatment of vascular hyporeactivity after shock.
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of the Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Liangming
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of the Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Gangming
authors.initials: G
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of the Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of the Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of the Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Jiatao
authors.initials: J
authors.lastname: Zang
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of the Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of the Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of the Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Lan
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of the Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, P. R. China. Electronic address: lt200132@163.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
mesh_terms: D000818:Animals; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D017538:Mesenteric Artery, Superior / Q000378:metabolism / Q000503:physiopathology; D018994:Myosin Light Chains / Q000378:metabolism*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012771:Shock, Hemorrhagic / Q000378:metabolism* / Q000503:physiopathology*; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D002148:Calmodulin-Binding Proteins; D004791:Enzyme Inhibitors; D055551:HSP27 Heat-Shock Proteins; C486114:Hspb1 protein, rat; D007093:Imidazoles; D018994:Myosin Light Chains; D010982:Platelet-Derived Growth Factor; D011725:Pyridines; D048049:Extracellular Signal-Regulated MAP Kinases; C093642:SB 203580
keywords: Caldesmon; HSP27; MLC20 phosphorylation; Shock; Vascular reactivity