Kietzmann T, Freimann S, Bratke J, Jungermann K
Institut für Biochemie und Moleculare Zellbiologie, Göttingen, Germany.
FEBS Lett. 1996 Jun 17;388(2-3):228-32. doi: 10.1016/0014-5793(96)00557-1.
Heme proteins acting as oxidases which produce H2O2 have been proposed to function as O2 sensors. In order to find out whether the modulation by O2 of PCK gene activation and the stimulation of the ALD A gene by venous O2 operate via H2O2, the effects of different concentrations of H2O2 and catalase as H2O2 scavenger were studied in rat hepatocyte cultures under different O2 tensions. Primary hepatocytes were treated with 0.1 nM glucagon, 50 microM H2O2 and/or 100 micrograms/ml catalase each at arterial O2 or venous pO2. PCK mRNA was induced by glucagon maximally under arterial O2 and only half maximally under venous O2. ALD A mRNA was induced only by venous O2. H2O2 enhanced the induction of PCK mRNA to similar levels under venous O2 tensions and the induction of ALD A mRNA under both O2 was completely inhibited. Addition of catalase antagonized the actions of H2O2 completely. These findings support the hypothesis that an H2O2-generating heme protein is involved in the O2 sensing system regulating gluconeogenic and glycolytic gene expression in response to O2.
作为产生过氧化氢的氧化酶的血红素蛋白已被提出可作为氧气传感器。为了探究氧气对磷酸烯醇式丙酮酸羧激酶（PCK）基因激活的调节作用以及静脉血氧对醛缩酶A（ALD A）基因的刺激作用是否通过过氧化氢发挥作用，我们在不同氧气张力下的大鼠肝细胞培养物中研究了不同浓度的过氧化氢和作为过氧化氢清除剂的过氧化氢酶的作用。原代肝细胞分别在动脉血氧或静脉血氧分压下用0.1 nM胰高血糖素、50 μM过氧化氢和/或100 μg/ml过氧化氢酶进行处理。在动脉血氧条件下，胰高血糖素可最大程度诱导PCK mRNA表达，而在静脉血氧条件下仅为最大诱导水平的一半。ALD A mRNA仅在静脉血氧条件下被诱导。过氧化氢在静脉血氧张力下可将PCK mRNA的诱导增强至相似水平，并且在两种血氧条件下ALD A mRNA的诱导均被完全抑制。添加过氧化氢酶可完全拮抗过氧化氢的作用。这些发现支持了这样一种假说，即一种产生过氧化氢的血红素蛋白参与了氧气传感系统，该系统可响应氧气调节糖异生和糖酵解基因的表达。
