HECTD1调控PI3K/AKT信号通路对低氧诱导的脑微血管内皮细胞损伤的影响  

Effects of HECTD1 on hypoxic-induced cerebral microvascular endothelial cell injury by regulating the PI3K/AKT signaling pathway

作　　者：梁碧娟 范云虎 黄云达 陶云仙 Liang Bijuan;Fan Yunhu;Huang Yunda;Tao Yunxian(Department of Geriatrics,the Second People's Hospital of Kunming,Yunnan 650000,China)

机构地区：[1]昆明市第二人民医院老年病科,云南650000 [2]云南大学附属医院神经内科 [3]云南省第三人民医院老年科 [4]曲靖六十九医院神经内科

出　　处：《脑与神经疾病杂志》2024年第5期265-271,共7页Journal of Brain and Nervous Diseases

基　　金：昆明市卫生健康委员会卫生科研课题(2022-03-10-007);昆明市卫生科技人才培养项目医学科技学科后备人才培养[2022-SW(后备)-46]。

摘　　要：目的探讨低氧应激下HECT结构域E3泛素连接酶1(HECTD1)对脑微血管内皮细胞(BMECs)的影响及其功能机制。方法BMECs细胞在1%O_(2)的条件下培养以诱导低氧刺激。使用多种细胞生物学功能实验测定来评估BMECs中低氧诱导的损伤。乳酸脱氢酶(LDH)、总抗氧化能力(T-AOC)、丙二醛(MDA)和超氧化物歧化酶(T-SOD)水平的检测以评估低氧诱导的氧化应激水平。Western blot检测PI3K/AKT信号通路相关蛋白的表达。结果在常氧条件下,过表达HECTD1可以提高BMECs的细胞活力。在低氧条件下,过表达HECTD1显著减轻了低氧诱导的细胞活力抑制作用。此外过表达HECTD1降低了低氧诱导的BMECs细胞凋亡和氧化应激。结论HECTD1通过阻断PI3K/AKT信号通路来保护BMECs免受低氧应激诱导的损伤,这表明HECTD1在低氧相关的脑疾病中具有治疗价值。Objective The role of HECTD1 in cardiovascular and cerebrovascular diseases is increasingly being revealed.The purpose of this study was to investigate the effect of HECTD1 on brain microvascular endothelial cells(BMECs)under hypoxia stress and its functional mechanism.Methods BMECs cells were cultured at 1%O_(2)to induce anoxic stimulation.Multiple cell biological function assays were used to evaluate hypoxia-induced injury in BMECs.Layereddoublehydroxides(LDH)、Total antioxidant capacity(T-AOC)、malondialdehyde(MD)and superoxide dismutase(T-SOD)levels were measured to assess the level of hypoxia-induced oxidative stress.Western blot was used to detect the expression of related proteins in PI3K/AKT signaling pathway.Results Overexpression of HECTD1 increased the cellular viability of BMECs under normal oxygen conditions.Overexpression of HECTD1 significantly mitigated the hypoxia-induced inhibition of cell viability under hypoxia conditions.In addition,overexpression of HECTD1 reduced hypoxic-induced apoptosis and oxidative stress of BMECs cells.Finally,we found that hypoxia induced PI3K/AKT signaling activation in BMECs cells.PI3K/AKT signaling pathway inhibitor LY294002 alleviates hypoxic-induced BMECs cell damage.Conclusion The HECTD1 protects BMECs from hypoxic stressinduced damage by blocking the PI3K/AKT signaling pathway,suggesting that the HECTD1 has therapeutic value in hypoxic-related brain diseases.

关 键 词：HECT结构域E3泛素连接酶1 PI3K/AKT信号通路 低氧 脑微血管内皮细胞 

分 类 号：R743[医药卫生—神经病学与精神病学]