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 language | English (US) |
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Pages (from-to) | 163-168 |
Number of pages | 6 |
Journal | Archives of Biochemistry and Biophysics |
Volume | 348 |
Issue number | 1 |
DOIs | |
State | Published - Dec 1 1997 |
Keywords
- Hypoxia
- Inflammation
- Ischemia- reperfusion
- Oxygen
- Regulation
- Superoxide
- Xanthine dehydrogenase
- Xanthine oxidase
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology