Changes in CLIP3 expression after sciatic nerve injury in adult rats

Changes in CLIP3 expression after sciatic nerve injury in adult rats
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DOI:
10.1007/s10735-012-9450-y
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发表时间:
2012-12-01
影响因子:
3.2
通讯作者:
Wang, Youhua
Wang, Youhua
中科院分区:
生物学4区
文献类型:
--
作者:
Deng, Xiaolong;Wei, Haixiang;Wang, Youhua

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CLIP 3(细胞质连接蛋白3)是一种547个氨基酸残基的细胞质蛋白,其定位于高尔基体堆叠和与高尔基体池并列的管泡元件。CLIP 3由三个Ank(锚蛋白)重复序列和两个CAP-Gly(细胞凋亡相关蛋白-甘氨酸)结构域组成,可能作为参与TGN-内体动力学的细胞质接头蛋白发挥作用。为了明确CLIP 3在周围神经系统变性和再生过程中的表达和作用,我们在成年大鼠中建立了急性坐骨神经损伤(SNI)模型。蛋白质印迹分析显示SNI后3天CLIP 3和PCNA(增殖细胞核抗原)蛋白水平显著上调。免疫组化结果显示,CLIP 3在损伤神经中的表达明显增加。免疫荧光进一步显示CLIP 3和PCNA蛋白分别与S100共定位于雪旺细胞的胞浆中。SC/神经元共培养物的表达谱表明,CLIP 3和PCNA蛋白水平在髓鞘形成的早期阶段显著表达。这些结果表明,CLIP 3可能与周围神经损伤后增殖的雪旺细胞的髓鞘形成和神经组织再生有关。CLIP 3和PCNA在早期髓鞘形成过程中的表达可能与雪旺细胞直接摄取和转运脂质和胆固醇有关,脂质和胆固醇来自于变性的髓鞘,为SNI后再生轴突周围髓鞘样结构的形成做准备。
CLIP3 (cytoplasmic linker protein 3) is a 547 amino acid residue cytoplasmic protein that localises to Golgi stacks and tubulovesicular elements juxtaposed to Golgi cisternae. Composed of three Ank (ankyrin) repeats and two CAP-Gly (cytoskeleton-associated protein-glycine) domains, CLIP3 may function as a cytoplasmic linker protein that is involved in TGN-endosome dynamics. To define the expression and role of CLIP3 during peripheral nervous system degeneration and regeneration, we created an acute sciatic nerve injury (SNI) model in adult rats. Western blot analyses revealed prominent up-regulation of CLIP3 and PCNA (proliferating cell nuclear antigen) protein levels at 3 days after SNI. Immunohistochemistry displayed that the expression of CLIP3 was noticeably increased in the injured nerve. Immunofluorescence further revealed that the CLIP3 and PCNA proteins colocalised respectively with S100 in the cytoplasm of Schwann cells. The expression profile of the SC/neuron co-cultures demonstrated that CLIP3 and PCNA protein levels were markedly expressed during the early stage of myelination. These results suggest that CLIP3 is likely associated with the myelination of proliferating Schwann cells, and nerve tissue regeneration after peripheral nerve injury. CLIP3 and PCNA expression during early myelination may be related to the direct uptake and transport of lipids and cholesterol, which were derived from the degenerating myelin, by Schwann cells to prepare for the formation of myelin sheath-like structures around regenerated axons after SNI.