Metal ions-stimulated iron oxidation in hydroxylases facilitates stabilization of HIF-1 alpha protein.

ABSTRACT: The exposure of cells to several metal ions stabilizes HIF-1 alpha protein. However, the molecular mechanisms are not completely understood. They may involve inhibition of hydroxylation by either substitution of iron by metal ions or by iron oxidation in the hydroxylases. Here we provide evidence supporting the latter mechanism. We show that HIF-1 alpha stabilization in human lung epithelial cells occurred following exposure to various metal and metalloid ions, including those that cannot substitute for iron in the hydroxylases. In each case addition of the reducing agent ascorbic acid (AA)* abolished HIF-1 alpha protein stabilization. To better understand the role of iron oxidation in hydroxylase inhibition and to define the role of AA in the enzyme recovery we applied molecular modeling

SUBMITTER: Kaczmarek M 

PROVIDER: S-EPMC2639755 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature