Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China; Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, China.
Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China.
Redox Biol. 2021 Nov;47:102154. doi: 10.1016/j.redox.2021.102154. Epub 2021 Sep 29.
Selenoprotein K (SELENOK), an endoplasmic reticulum (ER) resident protein, is regulated by dietary selenium and expressed at a relatively high level in neurons. SELENOK has been shown to participate in oxidation resistance, calcium (Ca) flux regulation, and the ER-associated degradation (ERAD) pathway in immune cells. However, its role in neurons has not been elucidated. Here, we demonstrated that SELENOK gene knockout markedly enhanced ER stress (ERS) and increased apoptosis in neurons. SELENOK gene knockout elicited intracellular Ca flux and activated the m-calpain/caspase-12 cascade, thus inducing neuronal apoptosis both in vivo and in vitro. In addition, SELENOK knockout significantly reduced cognitive ability and increased anxiety in 7-month-old mice. Our findings reveal an unexpected role of SELENOK in regulating ERS-induced neuronal apoptosis.
硒蛋白 K（SELENOK）是一种内质网（ER）驻留蛋白，受膳食硒的调节，在神经元中表达水平较高。研究表明，SELENOK 参与免疫细胞中的抗氧化、钙（Ca）流调节和 ER 相关降解（ERAD）途径。然而，其在神经元中的作用尚未阐明。在这里，我们证明了 SELENOK 基因敲除显著增强了神经元中的 ER 应激（ERS）并增加了细胞凋亡。SELENOK 基因敲除引起细胞内 Ca 流，并激活 m-calpain/caspase-12 级联反应，从而在体内和体外诱导神经元凋亡。此外，SELENOK 敲除显著降低了 7 月龄小鼠的认知能力并增加了其焦虑。我们的研究结果揭示了 SELENOK 在调节 ERS 诱导的神经元凋亡中的一个意想不到的作用。
