细胞色素b(5)中发挥着关键作用在人类微粒体铬(VI)的减少。
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迈尔斯Jannetto PJ, Antholine CR
细胞色素b(5)中发挥着关键作用在人类微粒体铬(VI)的减少。
毒理学。2001年2月28日,159(3):119 - 33所示。
- PubMed ID
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11223168 (在PubMed]
- 文摘
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铬(VI)的还原铬(III)导致活性中间体的形成导致细胞毒性、基因毒性、致癌性的铬(VI)含有的化合物。先前的研究表明,人类减少微粒体铬(VI)可能通过细胞色素b (5)。为了更好地理解人类的毒性铬(VI),细胞色素b的作用(5)结合P450还原酶检查在还原铬(VI)的转换。Proteoliposomes含重组人b细胞色素P450还原酶和(5)。P450还原酶的能力从NADPH协调高效的电子转移到细胞色素b(5)光谱分析证实了。NADPH-dependent铬(VI)还原速度由proteoliposomes当时比人类的微粒体。当这些率归一化等效细胞色素b(5)浓度,减少NADPH-dependent铬(VI)利率由人类微粒体在本质上是相同的proteoliposomes包含细胞色素b (5) + P450还原酶。Proteoliposomes只包含P450还原酶或细胞色素b(5)表现出可怜的铬(VI)减少功能。因为它先前表明,微量的铁(Fe)可以大大刺激减少微粒体铬(VI),铁的能力来刺激proteoliposomes减少铬(VI)的检查。氯化铁(FeCl(3))和铁腺苷二磷酸(FeADP)被证明刺激减少铬(VI); this stimulation could be abolished by the addition of deferoxamine, a specific Fe(III) chelator. The NADPH-dependent reduction rates of various ferric complexes by proteoliposomes were sufficient to account for the increased Cr(VI) reduction rates seen with the addition of FeCl(3) or FeADP. Cr(V) was detected by electron paramagnetic resonance (EPR) spectroscopy as a transient intermediate formed during NADPH-dependent Cr(VI) reduction mediated by proteoliposomes containing cytochrome b(5) and P450 reductase. Overall, cytochrome b(5) in combination with P450 reductase can account for the majority of the NADPH-dependent Cr(VI) reduction seen with human microsomes.