Distinct effects of contraction agonists on the phosphorylation state of cofilin in pulmonary artery smooth muscle.
Distinct effects of contraction agonists on the phosphorylation state of cofilin in pulmonary artery smooth muscle.
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DOI：
10.1155/2008/362741
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发表时间：
2008
影响因子：
--
通讯作者：
Yamboliev IA
中科院分区：
文献类型：
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作者：
Dai YP;Bongalon S;Mutafova-Yambolieva VN;Yamboliev IA
我们推测，激动剂诱导的收缩与肺动脉环(PA环)和培养的平滑肌细胞(PASMCs)的P-Cf/Cf比值有关。PA环用于等长收缩，并与PASMCs一起用等电聚焦和免疫印迹法测定P-CF/CF。在PA和分化型PASMCs中P-CF/CF值为22.5%，而在未分化的PASMCs中仅为14.8%。在PA的收缩反应相似的情况下，内皮素-1(100 NM)和去甲肾上腺素(1 μM)可使P-CF/CF增加2倍，而血管紧张素II(1 μM)则无此作用。所有激动剂均激活Rho-Kinase和LIMK2，抑制Rho-Kinase可消除激活。微囊藻毒素LF(20 NM)可增强血管紧张素II，但不能增强5-羟色胺(1 μM)介导的P-CF/CF升高。综上所述，所有受试激动剂都激活了Rho-Kinase-LIMK通路，并增加了P-CF/CF。血管紧张素II激活PP2A，并抵消LIMK介导的CF磷酸化。Cf磷酸化稳定外周肌动蛋白结构，可能有助于PA的最大收缩。
We hypothesized that agonist-induced contraction correlates with the phospho-cofilin/cofilin (P-CF/CF) ratio in pulmonary artery (PA) rings and cultured smooth muscle cells (PASMCs). PA rings were used for isometric contractions and along with PASMCs for assay of P-CF/CF by isoelectric focusing and immunoblotting. The P-CF/CF measured 22.5% in PA and differentiated PASMCs, but only 14.8% in undifferentiated PASMCs. With comparable contraction responses in PA, endothelin-1 (100 nM) and norepinephrine (1 μM) induced a 2-fold increase of P-CF/CF, while angiotensin II (1 μM) induced none. All agonists activated Rho-kinase and LIMK2, and activation was eliminated by inhibition of Rho-kinase. Microcystin LF (20 nM) potentiated the angiotensin II, but not the 5-hydroxytryptamine (1 μM)-mediated increase of P-CF/CF. In conclusion, all tested agonists activate the Rho-kinase-LIMK pathway and increase P-CF/CF. Angiotensin II activates PP2A and counteracts the LIMK-mediated CF phosphorylation. CF phosphorylation stabilizes peripheral actin structures and may contribute to the maximal contraction of PA.