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

  • Filomena G. Ottaviano
  • Shiow-Shih Tang
  • Diane E. Handy
  • Joseph Loscalzo
Article

Abstract

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.

Keywords

Antioxidant Selenocysteine 3′-untranslated region Regulation 

Abbreviations

GPx-3

Plasma glutathione peroxidase

UTR

3′-Untranslated region

SECIS

Selenocysteine insertion sequence

rGPx-3

Recombinant GPx-3

GPx

Glutathione peroxidase

GSH

Glutathione

Sec

Selenocysteine

eEFSec

Sec-elongation factor

SBP2

SECIS binding protein 2

qRT-PCR

Qualitative real-time polymerase chain reaction

SelD

Human selenophosphate synthetase D

G3PDH

Glyceraldehyde-3-phosphate dehydrogenase

rLacZ

Recombinant Lac Z

TRx

Thioredoxin

Notes

Acknowledgments

This work is supported by the National Institutes of Health grants HL61795, HL58976, HL28178, and HL81587. The authors would like to acknowledge and thank Barbara Voestch and Ying-Yi Zhang for their helpful advice and suggestions, and Stephanie Tribuna for excellent secretarial assistance.

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Filomena G. Ottaviano
    • 1
    • 2
  • Shiow-Shih Tang
    • 2
  • Diane E. Handy
    • 2
  • Joseph Loscalzo
    • 2
  1. 1.Whitaker Cardiovascular Institute and Evans Department of MedicineBoston University School of MedicineBostonUSA
  2. 2.Department of MedicineBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA

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