Elsevier

Redox Biology

Volume 47, November 2021, 102154
Redox Biology

Selenoprotein K deficiency-induced apoptosis: A role for calpain and the ERS pathway

https://doi.org/10.1016/j.redox.2021.102154Get rights and content
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Abstract

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 (Ca2+) 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 Ca2+ 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.

Keywords

SELENOK
Calpain
Endoplasmic reticulum stress
Neuronal apoptosis

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This work was supported by Shenzhen Fundamental Research Program (No. JCYJ20200109105836705), Guangdong Natural Science Foundation for Major Cultivation Project (2018B030336001), National Natural Sciences Foundation of China (Nos. 31800681), Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions (No. 2019SHIBS0003), NIAID/NIH grant R01AI089999.