MODIFICATION OF THE XANTHINE-CONVERTING ENZYME OF PERFUSED RAT-HEART DURING ISCHEMIA AND OXIDATIVE STRESS
MODIFICATION OF THE XANTHINE-CONVERTING ENZYME OF PERFUSED RAT-HEART DURING ISCHEMIA AND OXIDATIVE STRESS
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DOI：
10.1016/0891-5849(88)90024-x
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发表时间：
1988-01-01
影响因子：
7.4
通讯作者：
DILISA, F
中科院分区：
文献类型：
--
作者：
BINDOLI, A;CAVALLINI, L;DILISA, F
本文研究了缺血/再灌注及过氧化氢或联胺诱导的氧化应激过程中黄嘌呤脱氢酶向黄嘌呤氧化酶的可逆和不可逆转化及其与谷胱甘肽和蛋白SH基团的关系。各种形式的黄嘌呤转换酶的直接分光光度测量表明，在新鲜大鼠心脏或常氧灌注后，总是有一个基础水平的80%的黄嘌呤脱氢酶和20%的黄嘌呤氧化酶（15%不可逆和5%可逆），可能有助于自由基的背景生产。在缺血或药物再灌注过程中，不可逆的黄嘌呤氧化酶没有显著增加。全脑缺血后，可逆氧化酶几乎没有增加，而当缺血后再灌注时，可逆黄嘌呤氧化酶的增加有限（小于9%）。在后一种条件下，谷胱甘肽和SH基团分别减少约70%和25%。用氧化剂如过氧化氢（60 μ M）或二酰胺（100 μ M）灌注1小时确定黄嘌呤脱氢酶分别显著转化为约40%和60%的可逆黄嘌呤氧化酶;在从灌注介质中取出氧化剂后，该氧化酶活性部分地再转化为脱氢酶。在所有测试条件下，不可逆黄嘌呤氧化酶的水平保持不变。过氧化氢和二酰胺均诱导SH基团的强烈减少和谷胱甘肽的耗尽。黄嘌呤脱氢酶因此黄嘌呤氧化酶的转化似乎对巯基的氧化还原状态敏感。
The reversible and irreversible conversion of xanthine dehydrogenase to xanthine oxidase during ischemia/perfusion and oxidative stress induced by hydrogen peroxide or diamide and its relationship with glutathione and protein SH groups were studied. The direct spectrophotometric measurement of the various forms of the xanthine-converting enzyme indicates that, in the fresh rat heart or after normoxic perfusion, there always is a basal level of 80% xanthine dehydrogenase and 20% of xanthine oxidase (15% irreversible and 5% reversible) that could contribute to the background production of free radicals. There is no significant increase of irreversible xanthine oxidase during ischemia nor drug reperfusion. After global ischemia the reversible oxidase shows almost no increase while, when ischemia is followed by reperfusion, there is a limited increase (less than 9%) of the reversible xanthine oxidase. In the latter conditions there is a decrease of glutathione and of SH groups of about 70% and 25%, respectively. Perfusion for 1 h with oxidizing agents like hydrogen peroxide (60 .mu.M or diamide (100 .mu.M) determines a marked conversion of xanthine dehydrogenase to reversible xanthine oxidase of about 40% and 60% respectively; this oxidase activity partially reconverts to the dehydrogenase after withdrawing the oxidizing agents from the perfusion medium. The level of irreversible xanthine oxidase remains unchanged in all the conditions tested. Both hydrogen peroxide and diamide induce a strong decrease in SH groups and depletion of glutathione. The xanthine dehydrogenase .fwdarw. xanthine oxidase conversion thus appears to be sensitive to the redox state of thiol groups.