Contribution of reductase activity to quinone toxicity in three kinds of hepatic cells.
Contribution of reductase activity to quinone toxicity in three kinds of hepatic cells.
复制标题
还原酶活性对三种肝细胞醌毒性的贡献。
DOI：
10.1248/bpb.35.634
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发表时间：
2012
影响因子：
2
通讯作者：
N. Shimamoto
中科院分区：
文献类型：
--
作者：
Y. Ishihara;K. Tsuji;Satomi Ishii;Kyoko Kashiwagi;N. Shimamoto
有两种机制被提出来解释醌的细胞毒性：通过氧化还原循环的氧化应激和细胞内亲核试剂的芳基化。氧化还原循环是由细胞内还原酶催化的，因此氧化还原循环醌的毒性被认为与还原酶活性密切相关。本研究以3种肝细胞为研究对象，探讨了醌毒性与细胞内还原酶活性的关系；大鼠原代肝细胞HepG2和H4IIE。胞内还原酶活性为；原代肝细胞>>HepG2>H4IIE。这三种细胞对芳基化醌1,4-萘醌（NQ）表现出几乎相同的脆弱性。但对氧化还原循环醌2,3-二甲氧基-1,4-萘醌（DMNQ）的敏感性较低；主要肝细胞> HepG2 > H4IIE。此外，DMNQ引起的细胞毒性在HepG2细胞中显著减弱，在原代肝细胞中被还原酶抑制剂二苯四氯铵几乎完全抑制。这些数据表明，具有高还原酶活性的细胞易受氧化还原循环醌的影响。本研究为评估醌类药物在其发育过程中的毒性提供了必要的证据。
Two mechanisms have been proposed to explain quinone cytotoxicity: oxidative stress via the redox cycle, and the arylation of intracellular nucleophiles. The redox cycle is catalyzed by intracellular reductases, and therefore the toxicity of redox cycling quinone is considered to be closely associated with the reductase activity. This study examined the relationship between quinone toxicity and the intracellular reductase activity using 3 kinds of hepatic cells; rat primary hepatocytes, HepG2 and H4IIE. The intracellular reductase activity was; primary hepatocyte >>HepG2>H4IIE. The three kinds of cells showed almost the same vulnerability to an arylating quinone, 1,4-naphthoquinone (NQ). However, the susceptibility to a redox cycling quinone, 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) was; primary hepatocyte>HepG2>H4IIE. In addition, the cytotoxicity elicited by DMNQ was significantly attenuated in HepG2 cells and almost completely suppressed in primary hepatocytes by diphenyleneiodonium chloride, a reductase inhibitor. These data suggest that cells with a high reductase activity are susceptible to redox cycling quinones. This study provides essential evidence to assess the toxicity of quinone-based drugs during their developmental processes.
地塞米松、胰岛素和三碘甲状腺原氨酸对分离肝细胞原代培养物中微粒体 NADPH-细胞色素-c (P-450) 还原酶的影响。
DOI：
10.1016/0167-4889(87)90050-4
发表时间：
1987
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
vanderHoeven,T;Galivan,J
通讯作者：
Galivan,J