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Regulation of Cytochrome b5 Expression by miR-223 in Human Liver: Effects on Cytochrome P450 Activities

Regulation of Cytochrome b5 Expression by miR-223 in Human Liver: Effects on Cytochrome P450 Activities

Kei Takahashi, Yuki Oda, Yasuyuki Toyoda, Tatsuki Fukami, Tsuyoshi Yokoi, Miki Nakajima

Pharm Res. 2014 Mar;31(3):780-94.

PMID: 24078287

Abstract:

Purpose:
Cytochrome b5 (b5) is a hemoprotein that transfers electrons to several enzymes to fulfill functions in fatty acid desaturation, methemoglobin reduction, steroidogenesis, and drug metabolism. Despite the importance of b5, the regulation of b5 expression in human liver remains largely unknown. We investigated whether microRNA (miRNA) might be involved in the regulation of human b5.
Methods:
Twenty-four human liver specimens were used for correlation analysis. In silico analysis and luciferase assay were performed to determine whether the predicted miRNAs functionally target to b5. The miR-223 was overexpressed into HepG2 cells infected with adenovirus expressing human cytochrome P450.
Results:
In human livers, the b5 protein levels were not positively correlated with the b5 mRNA levels, and miR-223 levels were inversely correlated with the b5 mRNA levels or the translational efficiencies. The luciferase assay showed that miR-223 functionally binds to the element in the 3'-untranslated region of b5 mRNA. The overexpression of miR-223 significantly reduced the endogenous b5 protein level and the mRNA stability in HepG2 cells. Moreover, the overexpression of miR-223 significantly reduced CYP3A4-catalyzed testosterone 6β-hydroxylation activity and CYP2E1-catalyzed chlorzoxazone 6-hydroxylase activity but not CYP1A2-catalyzed 7-ethoxyresorufin O-deethylase activity.
Conclusions:
miR-223 down-regulates b5 expression in the human liver, modulating P450 activities.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4247578	Cytochrome b5 human			Price

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