Wang Da-Peng, Liu Ke-Jia, Kasper Graham, Lin Qi, Hai Jian
Department of Neurosurgery, Tong Ji Hospital, Tong Ji University School of Medicine, Shanghai 200065, China; Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, H3A 2B4, Canada.
Department of Cell Biology, Key Laboratory of Education Ministry for Cell Differentiation and Apoptosis, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Biomed Pharmacother. 2017 Jul;91:872-879. doi: 10.1016/j.biopha.2017.05.021. Epub 2017 May 11.
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.
慢性脑灌注不足（CCH）诱导的神经血管单元（NVU）破坏在各种神经系统疾病中广泛存在。小泛素样修饰特异性蛋白酶3（SENP3）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，SENP3是否参与CCH条件下的神经血管损伤仍不清楚。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的影响以及SENP3在此过程中的作用及其潜在机制。通过免疫化学检测SENP3的表达。通过蛋白质印迹分析和透射电子显微镜评估NVU的功能和结构。CCH导致SENP3上调、NVU内蛋白质水平的细胞和非细胞成分破坏以及超微结构恶化。用URB597治疗可逆转NVU损伤以及SENP3的过表达。这些结果揭示了URB597的一种新的神经保护作用，这表明URB597通过抑制SENP3改善CCH诱导的NVU损伤。
