CapZ dynamics are altered by endothelin-1 and phenylephrine via PIP2-and PKC-dependent mechanisms
CapZ dynamics are altered by endothelin-1 and phenylephrine via PIP2-and PKC-dependent mechanisms
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DOI：
10.1152/ajpcell.00544.2008
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发表时间：
2009-05-01
影响因子：
5.5
通讯作者：
Russell, Brenda
中科院分区：
文献类型：
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作者：
Hartman, Thomas J.;Martin, Jody L.;Russell, Brenda
Hartman TJ, Martin JL, Solaro RJ, Samarel AM, Russell B.内皮素-1和苯肾上腺素通过PIP2和pkc依赖机制改变CapZ动力学。[J] .中国生物医学工程学报，2009,31(6):1034- 1039。首次发表于2009年3月18日；doi: 10.1152 / ajpcell.00544.2008。肌肉肥大的一个悬而未决的问题是新的收缩单位是如何插入到一个稳定的现有细胞骨架网络中。CapZ对肌动蛋白封顶的调控可能在重塑过程中发挥作用，因此，在体外心脏细胞快速生长过程中确定了CapZ动力学。用表达绿色荧光蛋白- capz β 1的腺病毒感染新生大鼠心室肌细胞，对肥厚刺激反应正常。用内皮素-1 （100 nM）或苯肾上腺素（10 μ M）处理培养的肌细胞，荧光恢复分析光漂白后的CapZ动力学。内皮素治疗后30 s恢复明显。漂白后30分钟的分析显示，内皮素处理的capz感染细胞比对照组恢复更完全（77 +/- 9%比50 +/- 6%，P < 0.001）。苯肾上腺素组也有类似的结果（77±5%,P < 0.05）。研究了磷脂酰肌醇二磷酸（PIP2）介导内皮素和苯肾上腺素处理细胞中CapZ交换增加的潜在机制。用新霉素（500 μ M）隔离PIP2阻断内皮素（43 +/- 6%,P < 0.001）和苯肾上腺素（36 +/- 4%,P < 0.001）介导的恢复。蛋白激酶C抑制剂chelerythrine chloride （10 μ M）也阻断内皮素（53 +/- 10%,P < 0.001）和苯肾上腺素（42 +/- 3%,P < 0.001）介导的恢复。这项研究首次证明，内皮素和苯肾上腺素通过PIP2和pkc依赖性途径改变CapZ动力学，这可能破坏现有框架的稳定性，并允许肌体重构继续进行。
Hartman TJ, Martin JL, Solaro RJ, Samarel AM, Russell B. CapZ dynamics are altered by endothelin-1 and phenylephrine via PIP2 and PKC-dependent mechanisms. Am J Physiol Cell Physiol 296: C1034-C1039, 2009. First published March 18, 2009; doi:10.1152/ajpcell.00544.2008.-One of the unanswered questions in muscle hypertrophy is how new contractile units are inserted into a stable existing cytoskeletal meshwork. Regulation of actin capping by CapZ may play a role in remodeling processes, therefore, CapZ dynamics are determined during rapid growth of cardiac cells in vitro. Neonatal rat ventricular myocytes were infected with adenovirus expressing green fluorescent protein-CapZ beta 1 and responded normally to hypertrophic stimuli. CapZ dynamics were analyzed by fluorescence recovery after photobleaching in cultured myocytes treated with endothelin-1 (100 nM) or phenylephrine (10 mu M). Recovery by 30 s was greater with endothelin treatment. Analysis 30 min postbleach showed CapZ-infected cells treated with endothelin recovered more completely than controls (77 +/- 9% vs. 50 +/- 6%, P < 0.001). Similar results were found with phenylephrine (77 +/- 5%, P < 0.05). A potential mechanism for phosphatidylinositol bisphosphate (PIP2) mediation of increased CapZ exchange in endothelin-and phenylephrine-treated cells was tested. PIP2 sequestration with neomycin (500 mu M) blocked both endothelin-(43 +/- 6%, P < 0.001) and phenylephrine (36 +/- 4%, P < 0.001)-mediated recovery. The protein kinase C inhibitor chelerythrine chloride (10 mu M) also blocked endothelin-(53 +/- 10%, P < 0.001) and phenylephrine (42 +/- 3%, P < 0.001)-mediated recovery. This study demonstrates for the first time that endothelin and phenylephrine alter CapZ dynamics through PIP2- and PKC-dependent pathways, which might destabilize the existing framework and permit sarcomeric remodelling to proceed.