Inhibition of SENP3 by URB597 ameliorates neurovascular unit dysfunction in rats with chronic cerebral hypoperfusion.
Inhibition of SENP3 by URB597 ameliorates neurovascular unit dysfunction in rats with chronic cerebral hypoperfusion.
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DOI：
10.1016/j.biopha.2017.05.021
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发表时间：
2017-07
期刊：
影响因子：
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通讯作者：
Dapeng Wang;Ke-jia Liu;Graham Kasper;Qi Lin;J. Hai
中科院分区：
文献类型：
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作者：
Dapeng Wang;Ke-jia Liu;Graham Kasper;Qi Lin;J. Hai
由慢性脑灌注不足（CCH）引起的神经血管单位（NVU）的破坏已广泛发现于各种神经系统疾病中。SUMO特异性蛋白酶3（SENP 3）在神经元、星形胶质细胞和小胶质细胞中表达，并调节多种细胞事件。然而，SENP 3是否参与CCH条件下的神经血管损伤仍然是难以捉摸的。为了解决这个问题，我们研究了脂肪酸酰胺水解酶（FAAH）抑制剂URB597对NVU的影响和SENP 3在这个过程中的作用，以及潜在的机制。免疫组化法检测SENP 3的表达。免疫印迹分析和透射电镜观察NVU的结构和功能。CCH引起SENP 3的上调，NVU内蛋白质水平的细胞和非细胞组分的破坏，以及超微结构的恶化。用URB597处理可逆转NVU损伤以及SENP 3的过表达。这些结果揭示了URB597的一种新的神经保护作用，这暗示URB597通过抑制SENP 3来改善CCH诱导的NVU损伤。
Disruption of the neurovascular unit (NVU), induced by chronic cerebral hypoperfusion (CCH), has been broadly found in various neurological disorders. SUMO-specific protease 3 (SENP3) is expressed in neurons, astrocytes, and microglia, and regulates a variety of cell events. However, whether SENP3 is involved in neurovascular injury under the condition of CCH is still elusive. To address this issue, we investigated the effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597 on NVU and the role of SENP3 in this process, as well as the underling mechanisms. The expression of SENP3 was detected by immunochemistry. The function and structure of the NVU was assessed by Western blot analysis and transmission electron microscopy. CCH caused the upregulation of SENP3, the disruption of cell and non-cell components at the protein level within the NVU, and ultrastructural deterioration. The NVU impairment as well as overexpression of SENP3 were reversed by treatment with URB597. These results reveal a novel neuroprotective role in URB597, which implicates URB597 in the amelioration of CCH-induced NVU impairment by inhibiting SENP3.