Wan Hongzhi, Yang Ying, Li Miao, Liu Xin, Sun Yeying, Wang Kexin, Zhang Chunxiang, Zheng Qingyin, Wang Chaoyun
School of Pharmacy, Binzhou Medical University, Yantai, P. R. China.
Third class of senior high school, NO.2 Middle School of Yantai Shandong, Yantai, P. R. China.
Aging (Albany NY). 2019 Jul 23;11(14):5108-5123. doi: 10.18632/aging.102106.
Ischemia exerts a negative impact on mitochondrial function, which ultimately results in neuronal damage via alterations in gene transcription and protein expression. Long non- coding RNAs (LncRNAs) play pivotal roles in the regulation of target protein expression and gene transcription. In the present study, we observed the effect of an unclassical LncRNA AK005401on ischemia/reperfusion (I/R) ischemia-mediated hippocampal injury and investigated the regulatory role of fibroblast growth factor 21 (FGF21) and Yin Yang 1 (YY1). C57Black/6 mice were subjected to I/R using the bilateral common carotid clip reperfusion method, and AK005401 siRNA oligos were administered via intracerebroventricular injection. HT22 cells were used to establish a model of oxygen-glucose deprivation/reoxygenation (OGD/R). We observed pathological morphology and mitochondrial structure. Neuronal apoptosis was evident. Cell activity, cell respiration, FGF21, YY1, and antioxidant capacity were evaluated. I/R or OGD/R significantly increased the expressions of AK005401and YY1 and decreased FGF21expression, which further attenuated the activation of PI3K/Akt, promoted reactive oxygen species (ROS) generation, and then caused mitochondria dysfunction and cell apoptosis, which were reversed by AK005401 siRNA oligos and were aggravated by overexpression of AK005401 and YY1. We conclude that AK005401/YY1/FGF21 signaling pathway has an important role in I/R-mediated hippocampal injury.
缺血对线粒体功能产生负面影响，最终通过基因转录和蛋白质表达的改变导致神经元损伤。长链非编码RNA（LncRNAs）在靶蛋白表达和基因转录的调控中起关键作用。在本研究中，我们观察了非经典LncRNA AK005401对缺血/再灌注（I/R）介导的海马损伤的影响，并研究了成纤维细胞生长因子21（FGF21）和阴阳1（YY1）的调控作用。采用双侧颈总动脉夹闭再灌注法对C57BL/6小鼠进行I/R处理，并通过脑室内注射给予AK005401 siRNA寡核苷酸。利用HT22细胞建立氧糖剥夺/复氧（OGD/R）模型。我们观察了病理形态和线粒体结构。神经元凋亡明显。评估细胞活性、细胞呼吸、FGF21、YY1和抗氧化能力。I/R或OGD/R显著增加AK005401和YY1的表达，降低FGF21表达，进一步减弱PI3K/Akt的激活，促进活性氧（ROS）生成，进而导致线粒体功能障碍和细胞凋亡，AK005401 siRNA寡核苷酸可逆转这些变化，而AK005401和YY1的过表达则会加重这些变化。我们得出结论，AK005401/YY1/FGF21信号通路在I/R介导的海马损伤中起重要作用。
