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题名: CERKL interacts with mitochondrial TRX2 and protects retinal cells from oxidative stress-induced apoptosis
作者: Li, Chang1; Wang, Lei1; Zhang, Jing1, 2; Huang, Mi1; Wong, Fulton3, 4; Liu, Xuexue1; Liu, Fei1; Cui, Xiukun1; Yang, Guohua5; Chen, Jiaxiang1; Liu, Ying1; Wang, Jiuxiang1; Liao, Shengjie1; Gao, Meng1; Hu, Xuebin1; Shu, Xinhua6; Wang, Qing1; Yin, Zhan7; Tang, Zhaohui1; Liu, Mugen1
通讯作者: Liu, MG (reprint author), Huazhong Univ Sci & Technol, Ctr Human Genome Res, Key Lab Mol Biophys, Minist Educ, 1037 Luoyu Rd, Wuhan 430074, Hubei, Peoples R China.
关键词: CERKL ; TRX2 ; Oxidative stress ; Retina ; Apoptosis
刊名: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
发表日期: 2014-07-01
DOI: 10.1016/j.bbadis.2014.04.009
卷: 1842, 期:7, 页:1121-1129
收录类别: SCI
文章类型: Article
部门归属: [Li, Chang; Wang, Lei; Zhang, Jing; Huang, Mi; Liu, Xuexue; Liu, Fei; Cui, Xiukun; Chen, Jiaxiang; Liu, Ying; Wang, Jiuxiang; Liao, Shengjie; Gao, Meng; Hu, Xuebin; Wang, Qing; Tang, Zhaohui; Liu, Mugen] Huazhong Univ Sci & Technol, Ctr Human Genome Res, Key Lab Mol Biophys, Coll Life Sci & Technol,Minist Educ, Wuhan 430074, Hubei, Peoples R China; [Zhang, Jing] Henan Univ, Coll Med, Inst Immunol, Key Lab Cellular & Mol Immunol, Kaifeng 475004, Henan, Peoples R China; [Wong, Fulton] Duke Univ, Sch Med, Dept Ophthalmol, Durham, NC 27710 USA; [Wong, Fulton] Duke Univ, Sch Med, Dept Neurobiol, Durham, NC 27710 USA; [Yang, Guohua] Wuhan Univ, Sch Med, Dept Med Genet, Wuhan 430072, Hubei, Peoples R China; [Shu, Xinhua] Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland; [Yin, Zhan] Chinese Acad Sci, Inst Hydrobiol, Wuhan, Hubei, Peoples R China
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
资助者: National Natural Science Foundation of China [30771199, 81270983, 81371064]; Research Fund for the Doctoral Program of Higher Education of China [20120142110077]; Ministry of Education of the People's Republic of China [B08029]; National Key Technology R&D Program in the 12th Five year Plan of China [2012BAI09B04]
类目[WOS]: Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
摘要: Mutations in the ceramide kinase-like gene (CERKL) are associated with severe retinal degeneration. However, the exact function of the encoded protein (CERKL) remains unknown. Here we show that CERKL interacts with mitochondrial thioredoxin 2 (TRX2) and maintains TRX2 in the reduced redox state. Overexpression of CERKL protects cells from apoptosis under oxidative stress, whereas suppressing CERKL renders cells more sensitive to oxidative stress. In zebrafish, CERKL protein prominently locates in the outer segment and inner segment of the photoreceptor of the retina. Knockdown of CERKL in the zebrafish leads to an increase of retinal cell death, including cone and rod photoreceptor degeneration. Signs of oxidative damage to macromolecules were also detected in CERKL deficient zebrafish retina. Our results show that CERKL interacts with TRX2 and plays a novel key role in the regulation of the TRX2 antioxidant pathway and, for the first time, provides an explanation of how mutations in CERKL may lead to retinal cell death. (C) 2014 Elsevier B.V. All rights reserved.
英文摘要: Mutations in the ceramide kinase-like gene (CERKL) are associated with severe retinal degeneration. However, the exact function of the encoded protein (CERKL) remains unknown. Here we show that CERKL interacts with mitochondrial thioredoxin 2 (TRX2) and maintains TRX2 in the reduced redox state. Overexpression of CERKL protects cells from apoptosis under oxidative stress, whereas suppressing CERKL renders cells more sensitive to oxidative stress. In zebrafish, CERKL protein prominently locates in the outer segment and inner segment of the photoreceptor of the retina. Knockdown of CERKL in the zebrafish leads to an increase of retinal cell death, including cone and rod photoreceptor degeneration. Signs of oxidative damage to macromolecules were also detected in CERKL deficient zebrafish retina. Our results show that CERKL interacts with TRX2 and plays a novel key role in the regulation of the TRX2 antioxidant pathway and, for the first time, provides an explanation of how mutations in CERKL may lead to retinal cell death. (C) 2014 Elsevier B.V. All rights reserved.
关键词[WOS]: CERAMIDE KINASE-LIKE ; RECESSIVE RETINITIS-PIGMENTOSA ; CONE-ROD DYSTROPHY ; PHOTORECEPTOR DEGENERATION ; MACULAR DEGENERATION ; ER STRESS ; THIOREDOXIN ; GENE ; DEATH ; DAMAGE
语种: 英语
WOS记录号: WOS:000336698400024
ISSN号: 0925-4439
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/20081
Appears in Collections:水生生物分子与细胞生物学研究中心_期刊论文

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作者单位: 1.Huazhong Univ Sci & Technol, Ctr Human Genome Res, Key Lab Mol Biophys, Coll Life Sci & Technol,Minist Educ, Wuhan 430074, Hubei, Peoples R China
2.Henan Univ, Coll Med, Inst Immunol, Key Lab Cellular & Mol Immunol, Kaifeng 475004, Henan, Peoples R China
3.Duke Univ, Sch Med, Dept Ophthalmol, Durham, NC 27710 USA
4.Duke Univ, Sch Med, Dept Neurobiol, Durham, NC 27710 USA
5.Wuhan Univ, Sch Med, Dept Med Genet, Wuhan 430072, Hubei, Peoples R China
6.Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland
7.Chinese Acad Sci, Inst Hydrobiol, Wuhan, Hubei, Peoples R China

Recommended Citation:
Li, Chang; Wang, Lei; Zhang, Jing; Huang, Mi; Wong, Fulton; Liu, Xuexue; Liu, Fei; Cui, Xiukun; Yang, Guohua; Chen, Jiaxiang; Liu, Ying; Wang, Jiuxiang; Liao, Shengjie; Gao, Meng; Hu, Xuebin; Shu, Xinhua; Wang, Qing; Yin, Zhan; Tang, Zhaohui; Liu, Mugen.CERKL interacts with mitochondrial TRX2 and protects retinal cells from oxidative stress-induced apoptosis,BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE,2014,1842(7):1121-1129
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