Effect of Orexin-A on Mitochondrial Biogenesis, Mitophagy and Structure in HEK293-APPSWE Cell Model of Alzheimer’s Disease
Effect of Orexin-A on Mitochondrial Biogenesis, Mitophagy and Structure in HEK293-APPSWE Cell Model of Alzheimer’s Disease
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Orexin-A 对阿尔茨海默病 HEK293-APPSWE 细胞模型中线粒体生物合成、线粒体自噬和结构的影响
DOI：
10.1111/1440-1681.13424
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
ZhaoHong Xie
中科院分区：
文献类型：
--
作者：
Zhengyu Zhu;LinLin Xu;DeYan Cao;ChaoYuan Song;YuZhen Wang;Maoyu Li;Jieke Yan;ZhaoHong Xie
线粒体功能障碍在阿尔茨海默病（AD）的发病和进展中起着关键作用。我们前期的研究表明，AD相关突变型β-淀粉样前体蛋白（APP）的过度表达可导致线粒体生物发生和线粒体自噬异常，导致线粒体功能障碍。然而，其机制尚不清楚。在本研究中，我们研究了orexin-A.对AD相关突变APP细胞过表达的线粒体生物发生、线粒体自噬和线粒体结构的影响。我们用20 E2细胞作为AD细胞模型。20 E2细胞分别用orexin-A（50、100 nmol/L）处理。MTT法检测不同浓度的orexin-A对细胞活性的影响。与未处理的20 E2细胞相比，Orexin-A处理的20 E2细胞APP表达增加，细胞活力降低，三磷酸腺苷（ATP）水平降低，线粒体生物合成调节蛋白水平降低（过氧化物酶体增殖物激活受体γ共激活因子1-α [PGC-1α]，核呼吸因子1/2 [NRF 1/2]，线粒体转录因子A [TFAM]），线粒体自噬调节蛋白（Parkin，PTEN诱导的推定激酶1 [PINK 1]，微管相关蛋白轻链3 II/I [LC 3-II/LC 3-I]）水平升高，p62水平降低，线粒体结构受损。Orexin-A可能在AD时降低线粒体的生物合成，增强线粒体自噬，破坏线粒体结构。
Mitochondrial dysfunction plays a key role in the pathogenesis and progression of.Alzheimer's Disease (AD). Our previous studies showed that over expression of AD-.associated mutant β-amyloid precursor protein (APP) led to abnormalities of mito-.chondrial biogenesis and mitophagy, leading to mitochondrial dysfunction. However,.the mechanism remains unclear. In this study, we investigated the effect of orexin-A.on mitochondrial biogenesis, mitophagy and mitochondrial structure in overexpres-.sion of AD-associated mutant APP cells. We used 20E2 cells as the AD cell model..20E2 cells were treated with orexin-A (50, 100 nmol/L). The effect of different con-.centrations of orexin-A on cell activity was detected by MTT. As compared with the.non-treated 20E2 cells, orexin-A-treated 20E2 cells showed increased expression of.APP, decreased cell viability and decreased adenosine triphosphate (ATP) level, de-.creased levels of regulatory proteins of mitochondrial biogenesis (peroxisome prolif-.erator-activated receptor gamma coactivator 1-alpha [PGC-1α], nuclear respiratory.factor 1/2 [NRF1/2], mitochondrial transcription factor A [TFAM]), increased levels.of regulatory proteins of mitophagy (Parkin, PTEN-induced putative kinase 1 [PINK1],.microtubule-associated protein light chain 3 II/I [LC3-II/LC3-I]) and decreased p62.level, with damaged mitochondrial structure. Orexin-A may reduce mitochondrial.biogenesis, enhance mitophagy and damage mitochondrial structure in AD.