Srivastava M, Kale R K
Free Radical Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi-110 067, India.
Radiat Res. 2000 Jul;154(1):94-103. doi: 10.1667/0033-7587(2000)154[0094:roxosi]2.0.co;2.
The widely distributed xanthine oxidoreductase (XOR) system has been shown to be modulated upon exposure of animals to ionizing radiation through the conversion of xanthine dehydrogenase (XDH) into xanthine oxidase (XO). In the present work, radiomodification of the XOR system by phenylmethylsulfonyl fluoride (PMSF) and dithiothreitol (DTT) was examined using female Swiss albino mice which were irradiated with gamma rays at a dose rate 0.023 Gy s(-1). PMSF, a serine protease inhibitor, and DTT, the sulfhydryl reagent, were administered intraperitoneally prior to irradiation. The specific activities of XDH and XO as well as the XDH/XO ratio and the total activity (XDH+XO) were determined in the liver of the mice. The inhibition of XO activity, restoration of XDH activity, and increase in the XDH/XO ratio upon administration of PMSF were suggestive of irreversible conversion of XDH into XO mediated through serine proteases. The biochemical events required for the conversion were probably initiated during the early phase of irradiation, as the treatment with PMSF immediately after irradiation did not have a modulatory effect. Interestingly, DTT was not effective in modulating radiation-induced changes in the XOR system or oxidative damage in the liver of mice. The DTT treatment resulted in inhibition of the release of lactate dehydrogenase. However, the protection appears to be unrelated to the formation of TBARS. On the other hand, the presence of PMSF during irradiation inhibited radiation-induced oxidative damage and radiation-induced increases in the specific activity of lactate dehydrogenase. These findings suggest that a major effect of ionizing radiation is irreversible conversion of xanthine to xanthine oxidase.
广泛分布的黄嘌呤氧化还原酶（XOR）系统已被证明，当动物暴露于电离辐射时，通过黄嘌呤脱氢酶（XDH）转化为黄嘌呤氧化酶（XO）而受到调节。在本研究中，使用雌性瑞士白化小鼠，以0.023 Gy s(-1)的剂量率进行γ射线照射，研究了苯甲基磺酰氟（PMSF）和二硫苏糖醇（DTT）对XOR系统的辐射修饰作用。在照射前腹腔注射丝氨酸蛋白酶抑制剂PMSF和巯基试剂DTT。测定小鼠肝脏中XDH和XO的比活性以及XDH/XO比值和总活性（XDH+XO）。给予PMSF后，XO活性受到抑制，XDH活性恢复，XDH/XO比值增加，提示通过丝氨酸蛋白酶介导XDH不可逆地转化为XO。转化所需的生化事件可能在照射早期就已启动，因为照射后立即用PMSF处理没有调节作用。有趣的是，DTT在调节XOR系统的辐射诱导变化或小鼠肝脏的氧化损伤方面无效。DTT处理导致乳酸脱氢酶释放受到抑制。然而，这种保护作用似乎与丙二醛的形成无关。另一方面，照射期间PMSF的存在抑制了辐射诱导的氧化损伤和辐射诱导的乳酸脱氢酶比活性增加。这些发现表明，电离辐射的主要作用是黄嘌呤不可逆地转化为黄嘌呤氧化酶。
