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Constitutive Oxidative Stress by SEPHS1 Deficiency Induces Endothelial Cell Dysfunction

Authors
 Jisu Jung  ;  Yoomin Kim  ;  Jiwoon Na  ;  Lu Qiao  ;  Jeyoung Bang  ;  Dongin Kwon  ;  Tack-Jin Yoo  ;  Donghyun Kang  ;  Lark Kyun Kim  ;  Bradley A Carlson  ;  Dolph L Hatfield  ;  Jin-Hong Kim  ;  Byeong Jae Lee 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.22(21) : 11646, 2021-10 
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN
 1661-6596 
Issue Date
2021-10
Keywords
angiogenesis ; cell growth ; endothelial cell ; reactive oxygen species ; selenium ; selenophosphate synthetase ; selenoprotein
Abstract
The primary function of selenophosphate synthetase (SEPHS) is to catalyze the synthesis of selenophosphate that serves as a selenium donor during selenocysteine synthesis. In eukaryotes, there are two isoforms of SEPHS (SEPHS1 and SEPHS2). Between these two isoforms, only SEPHS2 is known to contain selenophosphate synthesis activity. To examine the function of SEPHS1 in endothelial cells, we introduced targeted null mutations to the gene for SEPHS1, Sephs1, in cultured mouse 2H11 endothelial cells. SEPHS1 deficiency in 2H11 cells resulted in the accumulation of superoxide and lipid peroxide, and reduction in nitric oxide. Superoxide accumulation in Sephs1-knockout 2H11 cells is due to the induction of xanthine oxidase and NADPH oxidase activity, and due to the decrease in superoxide dismutase 1 (SOD1) and 3 (SOD3). Superoxide accumulation in 2H11 cells also led to the inhibition of cell proliferation and angiogenic tube formation. Sephs1-knockout cells were arrested at G2/M phase and showed increased gamma H2AX foci. Angiogenic dysfunction in Sephs1-knockout cells is mediated by a reduction in nitric oxide and an increase in ROS. This study shows for the first time that superoxide was accumulated by SEPHS1 deficiency, leading to cell dysfunction through DNA damage and inhibition of cell proliferation.
Files in This Item:
T202105262.pdf Download
DOI
10.3390/ijms222111646
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kim, Lark Kyun(김락균) ORCID logo https://orcid.org/0000-0001-5983-4470
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/187194
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