Increased synaptophysin is involved in inflammation-induced heat hyperalgesia mediated by cyclin-dependent kinase 5 in rats.
Increased synaptophysin is involved in inflammation-induced heat hyperalgesia mediated by cyclin-dependent kinase 5 in rats.
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大鼠中突触素增加参与细胞周期蛋白依赖性激酶 5 介导的炎症引起的热痛觉过敏
DOI：
10.1371/journal.pone.0046666
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Yu BW
中科院分区：
文献类型：
--
作者：
Zhang HH;Zhang XQ;Wang WY;Xue QS;Lu H;Huang JL;Gui T;Yu BW
与细胞周期蛋白依赖性激酶5（CDK5）介导的炎症诱导的热痛觉过敏相关的机制仍然不确定。这项研究旨在检查CDK5是否通过与突触素蛋白相互作用，是通过与突触的膜蛋白相互作用，是由大鼠的脊髓背角介导了全外围辅助辅助（CFA），这是一种介导的膜蛋白，介导了内吞作用的囊肿囊泡的内细胞增多症。与突触前囊泡膜相关的分子标记。通过在CFA诱导的炎症性疼痛后的行为方法，成像研究和免疫沉淀的联合使用，检查了CDK5在介导突触素中的作用。结果表明，CDK5与突触素和可溶性N-乙基马来酰亚胺敏感因子（NSF）附着蛋白受体（SNARES）共定位，这些蛋白受体（SNARES）由大鼠脊髓角中的VAMP-2，SNAP-25和Synttaxin 1a组成。 CFA内注射后脊髓角神经元的突触素表达的增加，与持续6小时至3 d持续的热痛觉过敏的持续时间增加。鞘内给药Roscovitine是一种CDK5特异性抑制剂，在高温痛觉过敏和通过外周注射CFA诱导的热痛觉过敏过程中显着降低突触素的表达。本报告中提供的数据表明，CFA治疗后6小时的CALPAIN活性在先前的报告后暂时上调，表明Calpain能够将p35切割到P25中。其他实验室获得的先前研究的结果表明，在CFA处理的炎症性疼痛模型中未观察到脊髓角神经元内p35表达水平的显着变化，尽管观察到CDK5激酶的显着上调在2 h至7 d之间。因此，p25的产生以与CFA治疗的炎症性疼痛模型以calpain独立的方式发生。我们的结果表明，在CFA处理的大鼠的脊髓背角中介导的突触素水平升高参与了由CDK5介导的热痛觉过敏，这表明抑制CDK5突触的异常激活可能会带来减轻炎症性疼痛的新靶标。
Mechanisms associated with cyclin-dependent kinase 5 (Cdk5)-mediated heat hyperalgesia induced by inflammation remain undefined. This study was designed to examine whether Cdk5 mediates heat hyperalgesia resulting from peripheral injection of complete Freund's adjuvant (CFA) in the spinal dorsal horns of rats by interacting with synaptophysin, a well known membrane protein mediating the endocytosis-exocytosis cycle of synaptic vesicles as a molecular marker associated with presynaptic vesicle membranes. The role of Cdk5 in mediating synaptophysin was examined through the combined use of behavioral approaches, imaging studies, and immunoprecipitation following CFA-induced inflammatory pain. Results showed that Cdk5 colocalized with both synaptophysin and soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptors (SNAREs) consisting of VAMP-2, SNAP-25, and syntaxin 1A in spinal dorsal horn of rats. Increased synaptophysin expression of spinal cord horn neurons post intraplantar injection of CFA coincided with increased duration of heat hyperalgesia lasting from 6 h to 3 d. Intrathecal administration of roscovitine, a Cdk5 specific inhibitor, significantly depressed synaptophysin expression during peak heat hyperalgesia and heat hyperalgesia induced by peripheral injection of CFA. Data presented in this report indicated that calpain activity was transiently upregulated 6 h post CFA-treatment despite previous reports suggesting that calpain was capable of cleaving p35 into p25. Results from previous studies obtained by other laboratories demonstrated that significant changes in p35 expression levels within spinal cord horn neurons were not observed in the CFA-treated inflammatory pain model although significant upregulation of Cdk5 kinase was observed between 2 h to 7 d. Therefore, generation of p25 occurred in a calpain-independent fashion in a CFA-treated inflammatory pain model. Our results demonstrated that increased synaptophysin levels were involved in heat hyperalgesia mediated by Cdk5 in spinal cord dorsal horns of CFA-treated rats, suggesting that inhibiting abnormal activation of Cdk5-synaptophysin may present a novel target for diminishing inflammatory pain.
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影响因子：
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