| First Author | Wang H | Year | 2014 |
| Journal | J Neurochem | Volume | 131 |
| Issue | 1 | Pages | 4-11 |
| PubMed ID | 24947680 | Mgi Jnum | J:215315 |
| Mgi Id | MGI:5605109 | Doi | 10.1111/jnc.12795 |
| Citation | Wang H, et al. (2014) Hypoxia-inducible factor-1alpha mediates up-regulation of neprilysin by histone deacetylase-1 under hypoxia condition in neuroblastoma cells. J Neurochem 131(1):4-11 |
| abstractText | 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-1alpha gene increased NEP mRNA/protein levels, as well as enzyme activity while knockdown of HIF-1alpha decreased them. Meanwhile, HIF-1alpha 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-1alpha 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-1alpha binding to HDAC-1 at the early stage of hypoxia. |
