Zhang Ran, Liu Yun, Zhong Wenhua, Hu Zebo, Wu Chao, Ma Mengyao, Zhang Yi, He Xiangyun, Wang Lin, Li Shu, Hong Yun
Department of Pathophysiology, Wannan Medical College, Wuhu, China.
Department of Clinical, Wannan Medical College, Wuhu, China.
Front Pharmacol. 2022 May 2;13:683898. doi: 10.3389/fphar.2022.683898. eCollection 2022.
Previous studies have shown that Salt-induced kinase-2(SIK2) is involved in the regulation of various energy-metabolism-related reactions, and it also can regulate angiogenesis after cerebral ischemia-reperfusion. However, it is unclear whether SIK2 can regulate energy metabolism in cerebral ischemia-reperfusion injury. As mitochondria plays an important role in energy metabolism, whether SIK2 regulates energy metabolism through affecting mitochondrial changes is also worth to be explored. In this study, rats were treated with adeno-associated virus-SIK2-Green fluorescent protein (AAV-SIK2-GFP) for the overexpression of SIK2 before middle cerebral artery occlusion (MCAO). We found that SIK2 overexpression could alleviate the neuronal damage, reduce the area of cerebral infarction, and increase the adenosine triphosphate (ATP) content, which could promote the expression of phosphorylated-mammalian target of rapamycin-1 (p-mTORC1), hypoxia-inducible factor-1α (HIF-1α), phosphatase and tensin homologue-induced putative kinase 1 (PINK1) and E3 ubiquitinligating enzyme (Parkin). Transmission electron microscopy revealed that SIK2 overexpression enhanced mitochondrial autophagy. It is concluded that SIK2 can ameliorate neuronal injury and promote the energy metabolism by regulating the mTOR pathway during cerebral ischemia-reperfusion, and this process is related to mitochondrial autophagy.
先前的研究表明，盐诱导激酶2（SIK2）参与多种能量代谢相关反应的调节，并且它还能调节脑缺血再灌注后的血管生成。然而，尚不清楚SIK2是否能在脑缺血再灌注损伤中调节能量代谢。由于线粒体在能量代谢中起重要作用，SIK2是否通过影响线粒体变化来调节能量代谢也值得探讨。在本研究中，在大脑中动脉闭塞（MCAO）前，用腺相关病毒-SIK2-绿色荧光蛋白（AAV-SIK2-GFP）处理大鼠以过表达SIK2。我们发现，SIK2过表达可减轻神经元损伤，减少脑梗死面积，并增加三磷酸腺苷（ATP）含量，这可促进磷酸化雷帕霉素哺乳动物靶标-1（p-mTORC1）、缺氧诱导因子-1α（HIF-1α）、磷酸酶和张力蛋白同源物诱导的假定激酶1（PINK1）和E3泛素连接酶（Parkin）的表达。透射电子显微镜显示，SIK2过表达增强了线粒体自噬。结论是，SIK2可通过在脑缺血再灌注期间调节mTOR途径改善神经元损伤并促进能量代谢，并且这一过程与线粒体自噬有关。
