title: Mipu1, a novel direct target gene, is involved in hypoxia inducible factor 1-mediated cytoprotection.
abstract: Mipu1 (myocardial ischemic preconditioning up-regulated protein 1), recently identified in our lab, is a novel zinc-finger transcription factor which is up-regulated during ischemic preconditioning. However, it is not clear what transcription factor contributes to its inducible expression. In the present study, we reported that HIF-1 regulates the inducible expression of Mipu1 which is involved in the cytoprotection of HIF-1α against oxidative stress by inhibiting Bax expression. Our results showed that the inducible expression of Mipu1 was associated with the expression and activation of transcription factor HIF-1 as indicated by cobalt chloride (CoCl2) treatment, HIF-1α overexpression and knockdown assays. EMSA and luciferase reporter gene assays showed that HIF-1α bound to the hypoxia response element (HRE) within Mipu1 promoter region and promoted its transcription. Moreover, our results revealed that Mipu1 inhibited the expression of Bax, an important pro-apoptosis protein associated with the intrinsic pathway of apoptosis, elevating the cytoprotection of HIF-1 against hydrogen peroxide (H2O2)-mediated injury in H9C2 cells. Our findings implied that Bax may be a potential target gene of transcription factor Mipu1, and provided a novel insight for understanding the cytoprotection of HIF-1 and new clues for further elucidating the mechanisms by which Mipu1 protects cell against pathological stress.
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Kangkai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China ; Department of Pathology, the Affiliated Tumor Hospital, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Lei
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zou
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Anlan
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China ; Department of Endocrinology, the Second Xiangya hospital, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Xiaoliu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Zihui
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Xiao
mesh_terms: D000818:Animals; D002460:Cell Line; D003035:Cobalt / Q000494:pharmacology; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D000860:Hypoxia / Q000378:metabolism* / Q000382:microbiology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034622:RNA Interference; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C520710:Mipu1 protein, rat; D009687:Nuclear Proteins; D012097:Repressor Proteins; D051028:bcl-2-Associated X Protein; D003035:Cobalt; C018021:cobaltous chloride