Regulation of the extracellular antioxidant selenoprotein plasma glutathione peroxidase (GPx-3) in mammalian cells.

Published

Journal Article

Plasma glutathione peroxidase (GPx-3) is a selenocysteine-containing extracellular antioxidant protein that catalyzes the reduction of hydrogen peroxide and lipid hydroperoxides. Selenoprotein expression involves the alternate recognition of a UGA codon as a selenocysteine codon and requires signals in the 3'-untranslated region (UTR), including a selenocysteine insertion sequence (SECIS), as well as specific translational cofactors. To ascertain regulatory determinants of GPx-3 expression and function, we generated recombinant GPx-3 (rGPX-3) constructs with various 3'-UTR, as well as a Sec73Cys mutant. In transfected Cos7 cells, the Sec73Cys mutant was expressed at higher levels than the wild type rGPx-3, although the wild type rGPx-3 had higher specific activity, similar to plasma purified GPx-3. A 3'-UTR with only the SECIS was insufficient for wild type rGPx-3 protein expression. Selenocompound supplementation and co-transfection with SECIS binding protein 2 increased wild type rGPx-3 expression. These results demonstrate the importance of translational mechanisms in GPx-3 expression.

Full Text

Duke Authors

Cited Authors

  • Ottaviano, FG; Tang, S-S; Handy, DE; Loscalzo, J

Published Date

  • July 2009

Published In

Volume / Issue

  • 327 / 1-2

Start / End Page

  • 111 - 126

PubMed ID

  • 19219623

Pubmed Central ID

  • 19219623

Electronic International Standard Serial Number (EISSN)

  • 1573-4919

Digital Object Identifier (DOI)

  • 10.1007/s11010-009-0049-x

Language

  • eng

Conference Location

  • Netherlands