Deletion of the fih gene encoding an inhibitor of hypoxia-inducible factors increases hypoxia tolerance in zebrafish
Cai, Xiaolian1,4; Zhang, Dawei1; Wang, Jing1; Liu, Xing1; Ouyang, Gang1; Xiao, Wuhan1,2,3,4
2018-10-05
Source PublicationJOURNAL OF BIOLOGICAL CHEMISTRY
ISSN0021-9258
Volume293Issue:40Pages:15370-15380
AbstractMany aerobic organisms have developed molecular mechanism to tolerate hypoxia, but the specifics of these mechanisms remain poorly understood. It is important to develop genetic methods that confer increased hypoxia tolerance to intensively farmed aquatic species, as these are maintained in environments with limited available oxygen. As an asparaginyl hydroxylase of hypoxia-inducible factors (HIFs), factor inhibiting HIF (FIH) inhibits transcriptional activation of hypoxia-inducible genes by blocking the association of HIFs with the transcriptional coactivators CREB-binding protein (CBP) and p300. Therefore, here we sought to test whether fih is involved in regulating hypoxia tolerance in the commonly used zebrafish model. Overexpressing the zebrafish fih gene in epithelioma papulosum cyprini (EPC) cells and embryos, we found that fih inhibits the transcriptional activation of zebrafish HIF- proteins. Using CRISPR/Cas9 to obtain fih-null zebrafish mutants, we noted that the fih deletion makes zebrafish more tolerant of hypoxic conditions than their WT siblings, but does not result in oxygen consumption rates that significantly differ from those of WT fish. Of note, we identified fewer apoptotic cells in adult fih-null zebrafish brains and in fih-null embryos, possibly explaining why the fih-null mutant had greater hypoxia tolerance than the WT. Moreover, the fih deletion up-regulated several hypoxia-inducible genes in fih-null zebrafish exposed to hypoxia. The findings of our study suggest that fih plays a role in hypoxia tolerance by affecting the rate of cellular apoptosis in zebrafish.
SubtypeArticle
KeywordHypoxia Development Hydroxylase Zebrafish Stress Tolerance Fih Hif-1a Hif-1b Hif-2a Hif-2b Factor Inhibiting Hif
DOI10.1074/jbc.RA118.003004
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI
Funding OrganizationStrategic Priority Research Program of the Chinese Academy of Sciences(XDA08010208) ; NSFC(31830101 ; 91631102 ; 31671315 ; 31721005) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDA08010208) ; NSFC(31830101 ; 91631102 ; 31671315 ; 31721005)
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS KeywordHIGH-ALTITUDE ADAPTATION ; FACTOR 3A FOXO3A ; TRANSCRIPTIONAL ACTIVITY ; SIGNALING PATHWAY ; INDUCED AUTOPHAGY ; CELL-DEATH ; BECLIN 1 ; HYDROXYLASE ; PHYSIOLOGY ; FISHES
WOS IDWOS:000446549200004
Funding OrganizationStrategic Priority Research Program of the Chinese Academy of Sciences(XDA08010208) ; NSFC(31830101 ; 91631102 ; 31671315 ; 31721005) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDA08010208) ; NSFC(31830101 ; 91631102 ; 31671315 ; 31721005)
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/56032
Collection藻类生物学及应用研究中心_水生生物分子与细胞生物学研究中心
Affiliation1.Chinese Acad Sci, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Hubei, Peoples R China
2.Chinese Acad Sci, Key Lab Aquat Biodivers & Conservat, Inst Hydrobiol, Wuhan 430072, Hubei, Peoples R China
3.Minist Agr, Key Lab Aquaculture Dis Control, Wuhan 430072, Hubei, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
Recommended Citation
GB/T 7714
Cai, Xiaolian,Zhang, Dawei,Wang, Jing,et al. Deletion of the fih gene encoding an inhibitor of hypoxia-inducible factors increases hypoxia tolerance in zebrafish[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2018,293(40):15370-15380.
APA Cai, Xiaolian,Zhang, Dawei,Wang, Jing,Liu, Xing,Ouyang, Gang,&Xiao, Wuhan.(2018).Deletion of the fih gene encoding an inhibitor of hypoxia-inducible factors increases hypoxia tolerance in zebrafish.JOURNAL OF BIOLOGICAL CHEMISTRY,293(40),15370-15380.
MLA Cai, Xiaolian,et al."Deletion of the fih gene encoding an inhibitor of hypoxia-inducible factors increases hypoxia tolerance in zebrafish".JOURNAL OF BIOLOGICAL CHEMISTRY 293.40(2018):15370-15380.
Files in This Item:
File Name/Size DocType Version Access License
J. Biol. Chem.-2018-(852KB)期刊论文出版稿开放获取CC BY-NC-SAView Application Full Text
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Cai, Xiaolian]'s Articles
[Zhang, Dawei]'s Articles
[Wang, Jing]'s Articles
Baidu academic
Similar articles in Baidu academic
[Cai, Xiaolian]'s Articles
[Zhang, Dawei]'s Articles
[Wang, Jing]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Cai, Xiaolian]'s Articles
[Zhang, Dawei]'s Articles
[Wang, Jing]'s Articles
Terms of Use
No data!
Social Bookmark/Share
File name: J. Biol. Chem.-2018-Xiao-jbc.RA118.003004.pdf
Format: Adobe PDF
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.