| First Author | Kim HG | Year | 2008 |
| Journal | Biochem Biophys Res Commun | Volume | 369 |
| Issue | 2 | Pages | 666-71 |
| PubMed ID | 18295594 | Mgi Jnum | J:182491 |
| Mgi Id | MGI:5315694 | Doi | 10.1016/j.bbrc.2008.02.059 |
| Citation | Kim HG, et al. (2008) Metallothionein-III induces HIF-1alpha-mediated VEGF expression in brain endothelial cells. Biochem Biophys Res Commun 369(2):666-71 |
| abstractText | Metallothionein-III (MT-III), a metal-binding protein, is associated with resistance to neuronal injury. However, the underlying mechanism for its effects remains unclear. We therefore examined whether MT-III can induce VEGF expression and promote neuroprotective effects in brain endothelial bEND.3 cells. MT-III significantly induced VEGF mRNA and protein expression in bEND.3 cells in a dose- and time-dependent manner. Furthermore, MT-III treatment increased the stability of hypoxia-inducible factor 1alpha (HIF-1alpha) and stimulated transcription of a reporter gene under control of the VEGF promoter. MT-III also increased the accumulation of HIF-1alpha in nuclei and increased HIF-1alpha-binding to the VEGF promoter. MT-III increased PI3K/Akt and ERK1/2 phosphorylation according to Western blot analysis. However, pretreatment with PD98059 and LY294002 (ERK1/2 and Akt inhibitors) inhibited MT-III-induced stimulation of HIF-1alpha protein expression and VEGF production. These results suggest that MT-III upregulates VEGF production in brain endothelial cells by a HIF-1alpha-dependent mechanism. |
