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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Temporal-spatial expressions of p27kip1 and its phosphorylation on Serine-10 after acute spinal cord injury in adult rat: Implications for post-traumatic glial proliferation.
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Temporal-spatial expressions of p27kip1 and its phosphorylation on Serine-10 after acute spinal cord injury in adult rat: Implications for post-traumatic glial proliferation.

机译：成年大鼠急性脊髓损伤后p27kip1的时空表达及其在Serine-10上的磷酸化：对创伤后神经胶质增生的影响。

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摘要

P27kip1, as a member of Cip/Kip family of cyclin-dependent kinase inhibitors, plays important roles in cell cycle regulation and neurogenesis in the developing central nervous system. Serine-10 is the major phosphorylation site of p27kip1, and post-translational regulation of p27kip1 by different phosphorylation events is critical for its function. To elucidate the expressions and possible functions of p27kip1 and its phosphorylation in central nervous system lesion and repair, we performed an acute spinal cord contusion injury model in adult rats. Our work studied the temporal-spatial expression patterns of p27kip1 and Serine-10 phosphorylated p27kip1 (p-p27s10). Western blot analysis showed p27kip1 level significantly decreased at day 3 after damage, while p-p27s10 was detected at a high-level at the same time reaching the uninjured level. Moreover, immunofluorescence double labeling suggested these changes were striking in microglia and astrocytes, which were largely proliferated. Immunohistochemical analysis revealed subcellular localization changes of p27kip1 and p-p27s10 staining between nucleus and cytoplasm after injury in about 20% of total positive cells including neurons and glial cells. We also investigated the increased interactions of p27kip1 and p-p27s10 with CRM1 3 days after injury by co-immunoprecipitation studies. Taken together, we hypothesized spinal cord injury stimulated mitogenic signals to induce a serine-threonine kinase KIS (kinase interacting stathmin) to phosphorylate p27kip1 on Serine-10, so that p27kip1 could bind to CRM1 and be exported from nuclei for degradation. Such an event facilitated cell cycle progression of glial cells, especially microglia and astrocytes which had a prevalent proliferation.
机译：P27kip1，作为细胞周期蛋白依赖性激酶抑制剂的Cip / Kip家族的成员，在发育中的中枢神经系统的细胞周期调控和神经发生中起重要作用。丝氨酸10是p27kip1的主要磷酸化位点，通过不同的磷酸化事件对p27kip1的翻译后调控对其功能至关重要。为了阐明p27kip1的表达及其可能的功能及其在中枢神经系统损伤和修复中的磷酸化作用，我们在成年大鼠中建立了急性脊髓挫伤模型。我们的工作研究了p27kip1和Serine-10磷酸化的p27kip1（p-p27s10）的时空表达模式。蛋白质印迹分析表明，在损伤后第3天p27kip1水平显着降低，而同时检测到高水平的p-p27s10达到未损伤水平。此外，免疫荧光双重标记表明这些变化在小胶质细胞和星形胶质细胞中显着，它们在很大程度上增殖了。免疫组织化学分析显示，损伤后约20％的阳性细胞（包括神经元和神经胶质细胞）在细胞核与细胞质之间的p27kip1和p-p27s10染色亚细胞定位变化。我们还通过免疫共沉淀研究研究了损伤后3天p27kip1和p-p27s10与CRM1的相互作用增加。两者合计，我们假设脊髓损伤刺激有丝分裂信号，以诱导丝氨酸-苏氨酸激酶KIS（激酶相互作用的stathmin）磷酸化Serine-10上的p27kip1，从而使p27kip1可以与CRM1结合并从细胞核中输出进行降解。这种事件促进了具有普遍增殖的神经胶质细胞，特别是小胶质细胞和星形胶质细胞的细胞周期进程。

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