Selenoprotein K deficiency-induced apoptosis: A role for calpain and the ERS pathway
Shi-Zheng Jia,
Xin-Wen Xu,
Zhong-Hao Zhang,
Chen Chen,
Yu-Bin Chen,
Shao-Ling Huang,
Qiong Liu,
Peter R. Hoffmann,
Guo-Li Song
Affiliations
Shi-Zheng Jia
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
Xin-Wen Xu
Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China
Zhong-Hao Zhang
Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China; Shenzhen Bay Laboratory, Shenzhen, China
Chen Chen
Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China
Yu-Bin Chen
Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China
Shao-Ling Huang
Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China
Qiong Liu
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
Peter R. Hoffmann
Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA; Corresponding author.
Guo-Li Song
Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China; Shenzhen Bay Laboratory, Shenzhen, China; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China; Corresponding author. Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China.
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.
