ANTIOXIDANT ROLE OF CELLULAR REDUCED COENZYME-Q HOMOLOGS AND ALPHA-TOCOPHEROL IN FREE RADICAL-INDUCED INJURY OF HEPATOCYTES ISOLATED FROM RATS FED DIETS WITH DIFFERENT VITAMIN-E CONTENTS
ANTIOXIDANT ROLE OF CELLULAR REDUCED COENZYME-Q HOMOLOGS AND ALPHA-TOCOPHEROL IN FREE RADICAL-INDUCED INJURY OF HEPATOCYTES ISOLATED FROM RATS FED DIETS WITH DIFFERENT VITAMIN-E CONTENTS
复制标题
DOI：
10.1016/0005-2760(92)90232-k
复制
发表时间：
1992-08-19
期刊：
影响因子：
--
通讯作者：
KAWASAKI, T
中科院分区：
文献类型：
--
作者：
MATSURA, T;YAMADA, K;KAWASAKI, T
已知还原型辅酶Q9（CoQ 9 H2）和还原型辅酶Q10（CoQ 10 H2）以及α-生育酚（alpha-Toc）是哺乳动物组织中有效的脂溶性抗氧化剂。还原型辅酶Q同系物（CoQnH 2）似乎显示出独立于α-Toc的抗氧化活性（Matthias，T.，山田K.和川崎，T.（1992）Biochim. Biophys. Acta 1123，309-315）。为了进一步证实这一点，我们已经研究了细胞辅酶QnH 2和α-Toc的抗氧化作用，使用从喂食含有缺乏，充足和过量维生素E（VE）的饮食的大鼠中分离的肝细胞。用亲水性自由基引发剂2，2 '-偶氮二（2-脒基丙烷）二盐酸盐（AAPH）诱导细胞损伤。VE缺乏肝细胞中的α-Toc浓度约为VE充足肝细胞中的1/12，而VE过量肝细胞中的α-Toc浓度约为VE充足肝细胞中的7倍。在VE缺乏、充足和过量的细胞中，α-Toc与CoQnH 2（CoQ 9 H2加CoQ 10 H2）的摩尔比分别为0.03、0.33和2。在这三个饮食组的肝细胞中，α-Toc状态对辅酶Q同系物的浓度几乎没有影响。将这些肝细胞与50 mM AAPH孵育4 h。AAPH处理3 h后，各组肝细胞活力均迅速下降，且与脂质过氧化物的增加有关。VE缺陷细胞的细胞活力丧失和脂质过氧化反应的增加比其他两组的肝细胞更明显。AAPH处理后各组肝细胞内源性CoQ 9 H2含量呈线性下降，氧化型CoQ 9含量呈线性上升，而内源性CoQ 10 H2的下降幅度远小于内源性CoQ 9 H2的下降幅度。肝细胞的三个VE饮食组中的α-Toc在添加AAPH后也被消耗而没有时间滞后，并且CoQnH 2也不能幸免，即使在CoQnH 2浓度是α-Toc的38倍的VE缺陷细胞中也是如此。这些结果表明，CoQnH 2，特别是。辅酶Q9 H2是一种脂溶性抗氧化剂，在本研究所用的条件下，其在大鼠肝细胞中与α-Toc一样有效，并且独立于α-Toc发挥作用以抑制脂质过氧化。
Reduced coenzyme Q9 (CoQ9H2) and reduced coenzyme Q10 (CoQ10H2) as well as alpha-tocopherol (alpha-Toc) are known to be potent lipid-soluble antioxidants in mammalian tissues. Reduced coenzyme Q homolog (CoQnH2) appears to show antioxidant activity independent of that of alpha-Toc (Matsura, T., Yamada, K. and Kawasaki, T. (1992) Biochim. Biophys. Acta 1123, 309-315). To further confirm this, we have studied the antioxidant role of cellular CoQnH2 and alpha-Toc using hepatocytes isolated from rats fed diets containing deficient, sufficient, and excess amounts of vitamin E (VE). Cellular damage was induced with a hydrophilic radical initiator, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). The concentration of alpha-Toc in VE-deficient hepatocytes was approximately 1/12 that in VE-sufficient hepatocytes, whereas the concentration of alpha-Toc in VE-excess hepatocytes was approximately 7-fold that in VE-sufficient hepatocytes. The molar ratios of alpha-Toc to CoQnH2 (CoQ9H2 plus CoQ10H2) in VE-deficient, sufficient and excess cells were 0.03, 0.33 and 2, respectively. In the hepatocytes in these three dietary groups, alpha-Toc status had little effect on the concentration of CoQ homologs. These hepatocytes were incubated with 50 mM AAPH for 4 h. The cell viability in all groups of hepatocytes decreased rapidly after 3 h of AAPH treatment, and was associated with the increase of lipid peroxides. The loss of cell viability and the increase of lipid peroxidation in VE-deficient cells were more pronounced than those in the hepatocytes of the other two groups. The endogenous CoQ9H2 content of each group of hepatocytes decreased linearly with a reciprocal increase in oxidized CoQ9 after addition of AAPH, whereas the decrease of endogenous CoQ10H2 in each group during AAPH treatment was much less than that of endogenous CoQ9H2. Alpha-Toc in the three VE dietary groups of hepatocytes was also consumed without a time lag after addition of AAPH, and it was not spared by CoQnH2, even in VE-deficient cells where the CoQnH2 concentration was 38-fold that of alpha-Toc. These results indicate that CoQnH2, especially. CoQ9H2, is a lipid-soluble antioxidant, which is as effective as alpha-Toc in rat hepatocytes under the conditions employed in this study, and acts independently of alpha-Toc to inhibit lipid peroxidation.