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人类微粒体细胞色素 P450 酶在完整的裂殖酵母细胞内的无效循环。

Futile cycling by human microsomal cytochrome P450 enzymes within intact fission yeast cells.

机构信息

School of Pharmaceutical Science and Technology, Health Sciences Platform, Tianjin University, Tianjin, 300072, PR China.

Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, PR China.

出版信息

Arch Biochem Biophys. 2021 Apr 15;701:108791. doi: 10.1016/j.abb.2021.108791. Epub 2021 Feb 13.

DOI:10.1016/j.abb.2021.108791
PMID:33592181
Abstract

Human cytochrome P450 enzymes (CYPs or P450s) are known to be reduced by their electron transfer partners in the absence of substrate and in turn to reduce other acceptor molecules such as molecular oxygen, thereby creating superoxide anions (O). This process is known as futile cycling. Using our previously established fission yeast expression system we have monitored cells expressing each one of the 50 human microsomal CYPs in the absence of substrate for oxidation of dihydroethidium in living cells by flow cytometry. It was found that 38 of these display a statistically significant increase in O production. More specifically, cells expressing some CYPs were found to be intermediate strength O producers, which means that their effect was comparable to that of treatment with 3 mM HO. Cells expressing other CYPs had an even stronger effect, with those expressing CYP2B6, CYP5A1, CYP2A13, CYP51A1, or CYP1A2, respectively, being the strongest producers of O.

摘要

人细胞色素 P450 酶(CYPs 或 P450s)在没有底物的情况下,已知会被其电子转移伙伴还原,而反过来又会还原其他接受体分子,如分子氧,从而产生超氧阴离子(O)。这个过程被称为无效循环。使用我们之前建立的裂殖酵母表达系统,我们在没有底物的情况下监测了表达 50 种人类微粒体 CYP 中的每一种的细胞,以通过流式细胞术监测二氢乙啶在活细胞中的氧化。结果发现,其中 38 种显示出 O 产生的统计学上显著增加。更具体地说,表达某些 CYP 的细胞被发现是中等强度的 O 产生者,这意味着它们的效果可与用 3mM HO 处理相媲美。表达其他 CYP 的细胞具有更强的效果,分别表达 CYP2B6、CYP5A1、CYP2A13、CYP51A1 或 CYP1A2 的细胞是 O 的最强产生者。

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