PKC plays an important mediated effect in arginine vasopressin induced restoration of vascular responsiveness and calcium sensitization following hemorrhagic shock in rats.
PKC plays an important mediated effect in arginine vasopressin induced restoration of vascular responsiveness and calcium sensitization following hemorrhagic shock in rats.
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DOI：
10.1016/j.ejphar.2009.11.040
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发表时间：
2010-02
影响因子：
5
通讯作者：
Guangming Yang;Tao Li;Jing Xu;Liangming Liu
中科院分区：
文献类型：
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作者：
Guangming Yang;Tao Li;Jing Xu;Liangming Liu
本研究探讨蛋白激酶C（PKC）在精氨酸加压素（AVP）诱导的失血性休克血管反应性恢复和钙敏感化中的介导作用。以失血性休克大鼠离体肠系膜上级动脉和缺氧处理的血管平滑肌细胞（VSMC）为材料，研究了PKC-α、δ和ε亚型在AVP诱导血管反应性和钙敏感性恢复中的作用。同时观察其特异性抑制剂对VSMC肌球蛋白轻链磷酸酶（MLCP）、肌球蛋白轻链激酶（MLCK）活性及肌球蛋白轻链磷酸化（MLC 20）的影响。结果表明，AVP可增强失血性休克和缺氧后肠系膜上上级动脉和VSMC对去甲肾上腺素和钙离子的反应性。PKC-α抑制剂和PKC-ε抑制肽可拮抗AVP的上述作用，而PKC-δ抑制剂仅部分拮抗AVP的上述作用。AVP可上调缺氧VSMC颗粒组分中PKC-α和ε的表达，并降低MLCP活性，增加MLC 20磷酸化水平。AVP的这种作用可被PKC-α抑制剂和PKC-ε抑制肽抑制，而不被PKC-δ抑制剂抑制。提示PKC在AVP诱导失血性休克后血管反应性和钙敏感性恢复中起重要作用。PKC-α和ε可能是参与这一过程的主要亚型，并通过MLC 20磷酸化依赖机制发挥作用，而PKC-δ可能通过其他机制部分参与AVP的作用。
The present study investigated the mediated effect of protein kinase C (PKC) in arginine vasopressin (AVP)-induced restoration of vascular responsiveness and calcium sensitization following hemorrhagic shock. Using both isolated superior mesenteric artery from hemorrhagic shock rats and hypoxia-treated vascular smooth muscle cell (VSMC), we investigated the roles of PKC-α, δ and ε isoforms in AVP-induced restoration of vascular reactivity and calcium sensitivity. Meanwhile, effects of their specific inhibitors on the activity of myosin light chain phosphatase (MLCP), myosin light chain kinase (MLCK), and the phosphorylation of myosin light chain (MLC20) in VSMC were observed. The results indicated that AVP improved the reactivity of superior mesenteric artery and VSMC to norepinephrine and calcium following hemorrhagic shock and hypoxia. PKC-α inhibitor and PKC-ε inhibitory peptide antagonized these effects of AVP, while PKC-δ inhibitor only partially antagonized these effects of AVP. AVP up-regulated the expression of PKC-α and ε in the particulate fractions of hypoxia-treated VSMC with the decrease of the activity of MLCP and the increase of the phosphorylation of MLC20. These effects of AVP were inhibited by PKC-α inhibitor and PKC-ε inhibitory peptide, but not by the PKC-δ inhibitor. The results suggested that PKC plays an important role in AVP-induced restoration of vascular reactivity and calcium sensitivity following hemorrhagic shock. PKC-α and ε may be the main isoforms involved in this process and play effect via MLC20phosphorylation dependent mechanism, while PKC-δ may be partially involved in AVP action by other mechanisms.