REGULATION OF XANTHINE DEHYDROGENASE AND XANTHINE-OXIDASE ACTIVITY BYHYPOXIA

The present study determined the effect of hypoxia on xanthine dehydro genase (XDH) and xanthine oxidase (XO) activity and gene and protein e xpression in cultured bovine aortic endothelial cells (BAEC). BAEC wer e exposed to hypoxia (3% O-2) or anoxia (0% O-2) for 24 or 48 h and to 24 h of hypoxia followed by 24 h of reoxygenation. Hypoxia- and anoxi a-exposed BAEC demonstrated a greater than twofold increase in XDH/XO activity at 24 and 48 h compared with timed controls. Hypoxic cells th at were subsequently reoxygenated in 21% O-2 also demonstrated a simil ar increase in XDH/XO activity vs. timed controls. No differences were seen in mRNA levels at any time point. Similarly, no difference was n oted in XDH/XO protein expression after hypoxic exposure, as determine d by Western blot analysis. The increase in XDH/XO activity was not pr evented by cyclohexamide, indicating that protein synthesis was not re quired. Thus the increased XDH/XO activity observed in response to hyp oxia in the present study was due to posttranslational modulation of t he enzyme.