Analysis of the key networks,metabolic pathways,and regulation substances of hypoxia based on the omics and zebrafish model

Yi MA,Bin-bin XIA,Jing-yi LI,Zheng-chao XIA,Ping-xiang XU,LI Xiao-rong,Ming XUE

(Department of Pharmacology,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China)

T3-14

Analysis of the key networks,metabolic pathways,and regulation substances of hypoxia based on the omics and zebrafish model

Yi MA,Bin-bin XIA,Jing-yi LI,Zheng-chao XIA,Ping-xiang XU,LI Xiao-rong,Ming XUE

(Department of Pharmacology,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China)

OBJECTIVEHypoxia is associated with many complicated pathophysiological and biochemical processes that integrated and regulated via the key gene,protein and endogenous metabolite levels.Up to date,the exact molecular mechanism of hypoxia still remains unclear.In this work,we further explore the molecular mechanism of hypoxia and adaption to attenuate the damage in zebrafish model that have potential to resist hypoxic environment.METHODSThe hypoxic zebrafish model was established in different concentration of oxygen with 3%，5%，10%，21%in water.The brain tissue was separated and the RNA-seq was used to identify the differentially expressed genes.The related endogenous metabolites profiles were obtained by LC-HDMS,and the multivariate statistics was applied to discover the important metabolites candidates in hypoxic zebrafish.The candidates were searched in HMDB,KEGGand Lipid Maps databases.RESULTSThe zebrafish hypoxic model was successfully constructed via the different concentration of oxygen,temperature and hypoxic time.The activities of the related hypoxic metabolic enzymes and factors including HIF-1a,actate dehydrogenase(LDH)and citrate synthase(CS)were evaluated.Significant differences(P＜0.05 and fold change ＞2)in the expression of 422 genes were observed between the normal and 3%hypoxic model.Among them,201 genes increased depended on the lower concentration of oxygen.53 metabolites were identified that had significant difference between the hypoxia and control groups(P＜0.05,fold change＞1.5 and VIP＞1.5).The ten key metabolites were increased gradually while six compounds were decreased.The endogenous hypoxic metabolites of phenylalanine,D-glucosamine-6P and several important lipids with the relevant hub genes had similar change in hypoxic model.In addition,the metabolic pathways of phenylalanine,glutamine and glycolipid were influenced in both the levels of genes and metabolites.CONCLUSIONThe up-regulation of phenylalanine,D-glucosamine-6P and lipid may have further understanding of protective effect in hypoxia.Our data provided an insight to further reveal the hypoxia and adaptation mechanism.

hypoxia;adaptation;metabolic pathway;omics;zebrafish model

The project supported by National Natural Science Foundation of China(81573683 and 81173121)

Ming XUE,Tel:83911520,E-mail:xuem@ccmu.edu.cn