Constitutive Oxidative Stress by SEPHS1 Deficiency Induces Endothelial Cell Dysfunction

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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	selenium selenoprotein selenophosphate synthetase endothelial cell reactive oxygen species cell growth Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/fcf946c74f184f6fa9cbf931ace7d468
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spelling	oai:doaj.org-article:fcf946c74f184f6fa9cbf931ace7d4682021-11-11T17:07:06ZConstitutive Oxidative Stress by SEPHS1 Deficiency Induces Endothelial Cell Dysfunction10.3390/ijms2221116461422-00671661-6596https://doaj.org/article/fcf946c74f184f6fa9cbf931ace7d4682021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11646https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The 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, <i>Sephs1,</i> 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 <i>Sephs1</i>-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. <i>Sephs1</i>-knockout cells were arrested at G2/M phase and showed increased gamma H2AX foci. Angiogenic dysfunction in <i>Sephs1</i>-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.Jisu JungYoomin KimJiwoon NaLu QiaoJeyoung BangDongin KwonTack-Jin YooDonghyun KangLark Kyun KimBradley A. CarlsonDolph L. HatfieldJin-Hong KimByeong Jae LeeMDPI AGarticleseleniumselenoproteinselenophosphate synthetaseendothelial cellreactive oxygen speciescell growthBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11646, p 11646 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	selenium selenoprotein selenophosphate synthetase endothelial cell reactive oxygen species cell growth Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	selenium selenoprotein selenophosphate synthetase endothelial cell reactive oxygen species cell growth Biology (General) QH301-705.5 Chemistry QD1-999 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 Constitutive Oxidative Stress by SEPHS1 Deficiency Induces Endothelial Cell Dysfunction
description	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, <i>Sephs1,</i> 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 <i>Sephs1</i>-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. <i>Sephs1</i>-knockout cells were arrested at G2/M phase and showed increased gamma H2AX foci. Angiogenic dysfunction in <i>Sephs1</i>-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.
format	article
author	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
author_facet	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
author_sort	Jisu Jung
title	Constitutive Oxidative Stress by SEPHS1 Deficiency Induces Endothelial Cell Dysfunction
title_short	Constitutive Oxidative Stress by SEPHS1 Deficiency Induces Endothelial Cell Dysfunction
title_full	Constitutive Oxidative Stress by SEPHS1 Deficiency Induces Endothelial Cell Dysfunction
title_fullStr	Constitutive Oxidative Stress by SEPHS1 Deficiency Induces Endothelial Cell Dysfunction
title_full_unstemmed	Constitutive Oxidative Stress by SEPHS1 Deficiency Induces Endothelial Cell Dysfunction
title_sort	constitutive oxidative stress by sephs1 deficiency induces endothelial cell dysfunction
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/fcf946c74f184f6fa9cbf931ace7d468
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Constitutive Oxidative Stress by SEPHS1 Deficiency Induces Endothelial Cell Dysfunction

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