Hypoxia regulates xanthine dehydrogenase activity at pre- and posttranslational levels

Lance S. Terada, Dale Piermattei, Gayle N. Shibao, James L. McManaman, Richard M. Wright

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Hypoxia increases the activity of xanthine oxidase (XO) and its precursor, xanthine dehydrogenase (XDH), but the mechanism of regulation is unclear. In hypoxic Swiss 3T3 cells, an early (0-24 h) cycloheximide- insensitive increase in XO-XDH activity, coupled with a lack of increase in de novo XO-XDH synthesis (immunoprecipitation) or mRNA levels (quantitative RT-PCR), demonstrated a posttranslational effect of hypoxia. Similarly, hyperoxia decreased XO-XDH activity faster than could be accounted for by cessation of XO-XDH protein synthesis. In further support of a posttranslational effect, cells transfected with a constitutively driven XDH construct displayed an exaggerated increase in activity in hypoxia but no increase in activity in hyperoxia. However, more prolonged exposure to hypoxia (24-48 h) induced an increase in XO-XDH mRNA levels and de novo XO- XDH protein synthesis, suggesting an additional pretranslational effect. Finally, hypoxic induction of XO-XDH activity was found to be cell-type- restricted. We conclude that control of XO-XDH levels by oxygen tension is a complex process which involves several points of regulation.

Original languageEnglish (US)
Pages (from-to)163-168
Number of pages6
JournalArchives of Biochemistry and Biophysics
Volume348
Issue number1
DOIs
StatePublished - Dec 1 1997

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Keywords

  • Hypoxia
  • Inflammation
  • Ischemia- reperfusion
  • Oxygen
  • Regulation
  • Superoxide
  • Xanthine dehydrogenase
  • Xanthine oxidase

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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