title: Hypoxia-inducible factor-1α mediates up-regulation of neprilysin by histone deacetylase-1 under hypoxia condition in neuroblastoma cells.
abstract: Hypoxia-inducible factor (HIF)-1 is the key transcriptional activator mediating both adaptive and pathological responses to hypoxia. The purpose of this study was to find the role of HIF-1 in regulating neprilysin (NEP) at the early stage of hypoxia and explore the underlying mechanism. In this study, we demonstrated that both NEP mRNA and protein levels in neuroblastoma cells were elevated in early stages of hypoxia. Over-expression of HIF-1α gene increased NEP mRNA/protein levels, as well as enzyme activity while knockdown of HIF-1α decreased them. Meanwhile, HIF-1α was shown to bind to histone deacetylase (HDAC)-1 and reduced the association of HDAC-1 with NEP promoter, thus activating NEP gene transcription in a de-repression way. In summary, our results indicated that hypoxia in the early stages would up-regulate NEP expression, in which interaction of HIF-1α and HDAC-1 may play a role. This study suggested that NEP up-regulation might be an adaptive response to hypoxia, which was mediated by HIF-1α binding to HDAC-1 at the early stage of hypoxia.
authors.affiliation: Neuroscience Research Institute & Department of Neurobiology, Key Laboratory for Neuroscience, Ministry of Education & Ministry of Public Health, Health Science Center, Peking University, Beijing, China.
authors.forename: Hecheng
authors.initials: H
authors.lastname: Wang
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.forename: Huan
authors.initials: H
authors.lastname: Yang
authors.forename: Xiaosheng
authors.initials: X
authors.lastname: Tian
authors.forename: Yawei
authors.initials: Y
authors.lastname: Tong
authors.forename: Ting
authors.initials: T
authors.lastname: Zhou
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Yaoyun
authors.initials: Y
authors.lastname: Fu
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Guo
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Fan
authors.forename: Albert
authors.initials: A
authors.lastname: Yu
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
authors.forename: Xuefei
authors.initials: X
authors.lastname: Wu
authors.forename: Weizhong
authors.initials: W
authors.lastname: Xiao
authors.forename: Dehua
authors.initials: D
authors.lastname: Chui
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D005260:Female; D056284:Histone Deacetylase 1 / Q000096:biosynthesis*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015260:Neprilysin / Q000096:biosynthesis*; D009447:Neuroblastoma / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D015854:Up-Regulation / Q000502:physiology*
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D015260:Neprilysin; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1
keywords: Histone deacetylase-1; Hypoxia-inducible factor-1α; Neprilysin