Terada L S, Piermattei D, Shibao G N, McManaman J L, Wright R M
Webb-Waring Institute for Biomedical Research, University of Colorado Health Sciences Center, Denver 80262, USA.
Arch Biochem Biophys. 1997 Dec 1;348(1):163-8. doi: 10.1006/abbi.1997.0367.
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.
缺氧会增加黄嘌呤氧化酶（XO）及其前体黄嘌呤脱氢酶（XDH）的活性，但其调节机制尚不清楚。在缺氧的瑞士3T3细胞中，XO-XDH活性早期（0 - 24小时）出现对放线菌酮不敏感的增加，同时从头合成的XO-XDH（免疫沉淀法）或mRNA水平（定量逆转录聚合酶链反应）没有增加，这表明缺氧具有翻译后效应。同样，高氧降低XO-XDH活性的速度比因XO-XDH蛋白质合成停止所能解释的速度更快。为进一步支持翻译后效应，用组成型驱动的XDH构建体转染的细胞在缺氧时活性出现过度增加，但在高氧时活性没有增加。然而，更长时间暴露于缺氧（24 - 48小时）会诱导XO-XDH mRNA水平和从头合成的XO-XDH蛋白质增加，这表明存在额外的翻译前效应。最后，发现缺氧诱导XO-XDH活性具有细胞类型限制。我们得出结论，氧张力对XO-XDH水平的控制是一个复杂的过程，涉及多个调节点。
