| 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 | |
| Corresponding Author | Xiao, Wuhan(w-xiao@ihb.ac.cn) |
| 2018-10-05 | |
| Source Publication | JOURNAL OF BIOLOGICAL CHEMISTRY
 |
| ISSN | 0021-9258 |
| Volume | 293Issue:40Pages:15370-15380 |
| Abstract | Many 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. |
| Keyword | hypoxia development hydroxylase zebrafish stress tolerance fih hif-1a hif-1b hif-2a hif-2b factor inhibiting HIF |
| DOI | 10.1074/jbc.RA118.003004 |
| Funding Organization | Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; NSFC ; NSFC ; NSFC ; NSFC ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; NSFC ; NSFC ; NSFC ; NSFC ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; NSFC ; NSFC ; NSFC ; NSFC ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; NSFC ; NSFC ; NSFC ; NSFC |
| Indexed By | SCI ; SCI |
| Language | 英语 |
| Funding Project | Strategic Priority Research Program of the Chinese Academy of Sciences[XDA08010208] ; NSFC[31830101] ; NSFC[91631102] ; NSFC[31671315] ; NSFC[31721005] |
| WOS Research Area | Biochemistry & Molecular Biology |
| WOS Subject | Biochemistry & Molecular Biology |
| WOS ID | WOS:000446549200004 |
| WOS Keyword | HIGH-ALTITUDE ADAPTATION ; FACTOR 3A FOXO3A ; TRANSCRIPTIONAL ACTIVITY ; SIGNALING PATHWAY ; INDUCED AUTOPHAGY ; CELL-DEATH ; BECLIN 1 ; HYDROXYLASE ; PHYSIOLOGY ; FISHES |
| Publisher | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
| Funding Organization | Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; NSFC ; NSFC ; NSFC ; NSFC ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; NSFC ; NSFC ; NSFC ; NSFC ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; NSFC ; NSFC ; NSFC ; NSFC ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; NSFC ; NSFC ; NSFC ; NSFC |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.ihb.ac.cn/handle/342005/29171 |
| Collection | 水生生物分子与细胞生物学研究中心_期刊论文 |
| Corresponding Author | Xiao, Wuhan |
| Affiliation | 1.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. |
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