Deletion of the fih gene encoding an inhibitor of hypoxia-inducible factors increases hypoxia tolerance in zebrafish

doi:10.1074/jbc.RA118.003004

CORC > 水生生物研究所 > 中科院水生所知识产出（2009年前） > 水生生物分子与细胞生物学研究中心 > 期刊论文

	Deletion of the fih gene encoding an inhibitor of hypoxia-inducible factors increases hypoxia tolerance in zebrafish
	Cai, Xiaolian 1,4; Zhang, Dawei 1; Wang, Jing 1; Liu, Xing 1; Ouyang, Gang 1; Xiao, Wuhan 1,2,3,4
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2018-10-05
卷号	293 期号:40 页码:15370-15380
关键词	hypoxia development hydroxylase zebrafish stress tolerance fih hif-1a hif-1b hif-2a hif-2b factor inhibiting HIF
ISSN号	0021-9258
DOI	10.1074/jbc.RA118.003004
通讯作者	Xiao, Wuhan(w-xiao@ihb.ac.cn)
英文摘要	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.
资助项目	Strategic Priority Research Program of the Chinese Academy of Sciences[XDA08010208] ; NSFC[31830101] ; NSFC[91631102] ; NSFC[31671315] ; NSFC[31721005]
WOS关键词	HIGH-ALTITUDE ADAPTATION ; FACTOR 3A FOXO3A ; TRANSCRIPTIONAL ACTIVITY ; SIGNALING PATHWAY ; INDUCED AUTOPHAGY ; CELL-DEATH ; BECLIN 1 ; HYDROXYLASE ; PHYSIOLOGY ; FISHES
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
WOS记录号	WOS:000446549200004
资助机构	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
内容类型	期刊论文
源URL	[http://ir.ihb.ac.cn/handle/342005/29170]
专题	水生生物研究所_水生生物分子与细胞生物学研究中心_期刊论文
通讯作者	Xiao, Wuhan
作者单位	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
推荐引用方式 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.