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α-晶状体蛋白通过调节 RhoA/rock/丝切蛋白/MLC 信号通路促进大鼠轴突再生。

α-Crystallin promotes rat axonal regeneration through regulation of RhoA/rock/cofilin/MLC signaling pathways.

机构信息

Southwest Hospital, Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, People's Republic of China.

出版信息

J Mol Neurosci. 2012 Jan;46(1):138-44. doi: 10.1007/s12031-011-9537-z. Epub 2011 May 17.

DOI:10.1007/s12031-011-9537-z
PMID:21584655
Abstract

Intravitreal injection of α-crystallin can promote axons from optic nerve regeneration after crushing in rats. We have previously demonstrated that α-crystallin can counteract the effect of myelin inhibitory factors and stimulate neurite growth. And a common crucial signaling event for myelin inhibitory factors is the activation of RhoA. To investigate whether α-crystallin counteracts the inhibitory effect of myelin inhibitory factors through regulation of RhoA/Rock signaling pathway, α-crystallin (10(-4) g/L) was injected into rat vitreous at the time the optic nerve crushed. The RhoA protein activity and the expression of RhoA and Rock were evaluated after 3 days of optic nerve axotomy. Rock downstream effectors, phosphorylated cofilin, and phosphorylated myosin light chain were detected when retinal neurons were cultured for 3 days. Axonal regeneration and neurites growth of cultured cells were observed also. Our results showed that α-crystallin decreased the RhoA protein activity and the phosphorylation of both cofilin and myosin light chain, and promoted the axonal growth. However, the expression of RhoA and Rock was not affected by α-crystallin. These findings indicated that α-crystallin could counteract the effect of myelin inhibitory factors through the regulation of RhoA/Rock signaling pathway.

摘要

玻璃体内注射α-晶体蛋白可促进大鼠视神经挤压后轴突再生。我们之前的研究表明,α-晶体蛋白可以对抗髓鞘抑制因子的作用,刺激神经突生长。髓鞘抑制因子的一个常见关键信号事件是 RhoA 的激活。为了研究α-晶体蛋白是否通过调节 RhoA/Rock 信号通路来对抗髓鞘抑制因子的抑制作用,在视神经挤压时向大鼠玻璃体中注射 10(-4)g/L 的α-晶体蛋白。视神经切断 3 天后,评估 RhoA 蛋白活性以及 RhoA 和 Rock 的表达。当视网膜神经元培养 3 天时,检测 Rock 下游效应物磷酸化丝切蛋白和磷酸化肌球蛋白轻链。还观察了培养细胞的轴突再生和神经突生长。我们的结果表明,α-晶体蛋白降低了 RhoA 蛋白活性以及丝切蛋白和肌球蛋白轻链的磷酸化水平,促进了轴突生长。然而,α-晶体蛋白对 RhoA 和 Rock 的表达没有影响。这些发现表明,α-晶体蛋白可以通过调节 RhoA/Rock 信号通路来对抗髓鞘抑制因子的作用。

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Ophthalmic Res. 2011;45(3):164-8. doi: 10.1159/000319944. Epub 2010 Sep 30.
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αA-Crystallin associates with α6 integrin receptor complexes and regulates cellular signaling.αA-晶体蛋白与α6 整合素受体复合物结合,调节细胞信号转导。
Exp Eye Res. 2010 Nov;91(5):640-51. doi: 10.1016/j.exer.2010.08.006. Epub 2010 Aug 13.
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In vitro study of the effects of lens extract on rat retinal neuron survival and neurite outgrowth.
氟尿嘧啶加剧三阴性乳腺癌细胞系中α-晶体蛋白 B 链介导的细胞迁移。
Sci Rep. 2023 Mar 10;13(1):4010. doi: 10.1038/s41598-023-31186-7.
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Histological and Top-Down Proteomic Analyses of the Visual Pathway in the Cuprizone Demyelination Model.铜螯合剂诱导脱髓鞘模型中视觉通路的组织学和自上而下蛋白质组学分析
J Mol Neurosci. 2022 Jun;72(6):1374-1401. doi: 10.1007/s12031-022-01997-w. Epub 2022 May 30.
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Role of ATP-Small Heat Shock Protein Interaction in Human Diseases.ATP与小分子热休克蛋白相互作用在人类疾病中的作用。
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