- 作者：Liangming Liu ; MD ; PhD ; Gangming Yang ; MD ; Yu Zhu ; BA ; Jing Xu ; MD ; Jiatao Zang ; MD ; Jie Zhang ; MS ; Xiaoyong Peng ; BA ; Dan Lan ; BA ; Tao Li ; MD ; lt200132@163.com" class="auth_mail
- 关键词：Shock ; Vascular reactivity ; MLC20 phosphorylation ; Caldesmon ; HSP27
- 刊名：Journal of Surgical Research
- 出版年：April, 2014
- 年：2014
- 卷：187
- 期：2
- 页码：571-580
- 全文大小：1483 K
class="h4">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.class="h4">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.
class="h4">Results
PDGF (40-100聽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聽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.
class="h4">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.