Regulation of cholesterol biosynthesis and metabolismin Hep G2 cells by δ8(14)-15-ketoergostane derivatives | Zendy

Arif R. Mehtiev | Zendy; V.I. Fedchenko | Zendy; Ya. V. Tkachev | Zendy; Vladimir P. Timofeev | Zendy; A. Yu. Misharin | Zendy

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Regulation of cholesterol biosynthesis and metabolismin Hep G2 cells by δ8(14)-15-ketoergostane derivatives

Author(s) -

Arif R. Mehtiev,

V.I. Fedchenko,

Ya. V. Tkachev,

Vladimir P. Timofeev,

A. Yu. Misharin

Publication year - 2010

Publication title -

biomeditsinskaya khimiya

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.192

H-Index - 15

eISSN - 2310-6972

pISSN - 2310-6905

DOI - 10.18097/pbmc20105605576

Subject(s) - biosynthesis , reductase , chemistry , sterol , cyp3a4 , hep g2 , biochemistry , cyp27a1 , cholesterol , hmg coa reductase , stereochemistry , enzyme , cytochrome p450 , in vitro

The comparative study of effects of 5α-cholest-8(14)-en-15-on-3β-ol (I), (22E)-5α-ergosta-8(14),22-dien-15-on-3β-ol (II), (22S,23S)-22,23-oxido-5α-ergost-8(14)-en-15-on-3β-ol (III) and (22R,23R)-22,23-oxido-5α-ergost-8(14)-en-15-on-3β-ol (IV) on HMG-CoA reductase, CYP27A1 and CYP3A4 genes expression in Hep G2 cells was performed. In the contrast to 15-ketocholestane derivative (I), 15-ketoergostane derivatives (II - IV) decreased the HMG- CoA reductase mRNA level; (22R,23R)-22,23-oxido-5α-ergost-8(14)-en-15-on-3β-ol (IV) significantly increased CYP3A4 mRNA level (320% from control). Ketosterol (II) was found to be a more potent inhibitor of cholesterol biosynthesis in Hep G2 cells at a prolong incubation, compared with ketosterol (I). The side chain conformation of compounds (I) - (IV) was evaluated by computational modeling; the correlation between biological activity of these compounds and conformational flexibility of their side chains was found. The results obtained indicated that Δ8(14)-15-ketoergostane derivatives may be used as a sterol biosynthesis and metabolism regulators in liver cells.

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