A comparative study of the conversion of 7-hydroxycholesterol in rabbit, guinea pig, rat, hamster, and chicken

Maeda, Yorio; Nagatomo, Hidehito; Uchiyama, Fujio; Nagatomo, Junji; Yamada, Manabu; Shiotsuki, Hironori; Ohta, Yoshikazu; Sato, Shingo; Kai, Masahiro; Kondo, Kazuhiro; Higashi, Shinji; Setoguchi, Toshiaki

doi:10.1016/s0039-128x(02)00027-2

Cited by 15 publications

(13 citation statements)

References 16 publications

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“…They observed the oxidation of 7␣-hydroxycholesterol to 7KC by hamster and chicken but not rat, rabbit, or guinea pig liver microsomes and conversion of 7␤-hydroxycholesterol to 7KC in all species except guinea pig. Importantly, Maeda et al (17) report the reduction of 7KC to both 7␣-hydroxycholesterol and 7␤-hydroxycholesterol in equal amounts by hamster liver microsomes, consistent with the activities of recombinant hamster 11␤-HSD1 obtained in the present study. This is, however, in contrast to Song et al (16), reporting only oxidation of 7-hydroxycholesterols.…”

Section: -Ketocholesterol Reduction By 11␤-hsd1supporting

confidence: 91%

“…The cloning of hamster 11␤-HSD1 and its comparison with the rat and human enzyme explains part of the species-specific differences in the interconversion of 7-hydroxycholesterol and 7KC observed by Maeda et al (17). They observed the oxidation of 7␣-hydroxycholesterol to 7KC by hamster and chicken but not rat, rabbit, or guinea pig liver microsomes and conversion of 7␤-hydroxycholesterol to 7KC in all species except guinea pig.…”

Section: -Ketocholesterol Reduction By 11␤-hsd1mentioning

confidence: 90%

“…These results indicate an essential role for sterol 27-hydroxylase in the metabolism of 7KC in macrophagefoam cells. However, a recent study in sterol 27-hydroxylasedeficient mice demonstrated efficient hepatic metabolism of 7KC (15), thus indicating that another enzyme must be involved in the initial step of 7KC metabolism in the liver.In addition to the formation of 7KC by auto-oxidation or its uptake from food, recent evidence from experiments with purified protein and liver microsomal fractions suggest that 7KC may be formed enzymatically from either 7␤-hydroxycholesterol or 7␣-hydroxycholesterol in various species (16,17). Song et al (16) purified an enzyme from hamster liver microsomes, which efficiently converted both 7␣-hydroxycholesterol and 7␤-hydroxycholesterol to 7KC.…”

mentioning

confidence: 99%

“…In addition to the formation of 7KC by auto-oxidation or its uptake from food, recent evidence from experiments with purified protein and liver microsomal fractions suggest that 7KC may be formed enzymatically from either 7␤-hydroxycholesterol or 7␣-hydroxycholesterol in various species (16,17). Song et al (16) purified an enzyme from hamster liver microsomes, which efficiently converted both 7␣-hydroxycholesterol and 7␤-hydroxycholesterol to 7KC.…”

mentioning

confidence: 99%

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Rapid Hepatic Metabolism of 7-Ketocholesterol by 11β-Hydroxysteroid Dehydrogenase Type 1

Schweizer

Zürcher

Balázs

et al. 2004

Journal of Biological Chemistry

119

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The role of 11␤-hydroxysteroid dehydrogenase type 1 (11␤-HSD1) in the local activation of the glucocorticoid receptor by converting inactive 11-ketoglucocorticoids to active 11␤-hydroxyglucocorticoids is well established. Currently, 11␤-HSD1 is considered a promising target for treatment of obese and diabetic patients. Here, we demonstrate a role of 11␤-HSD1 in the metabolism of 7-ketocholesterol (7KC), the major dietary oxysterol. Comparison of recombinant 11␤-HSD1, transiently expressed in human embryonic kidney 293 cells, revealed the stereo-specific interconversion of 7KC and 7␤-hydroxycholesterol by rat and human 11␤-HSD1, whereas the hamster enzyme interconverted 7␣-hydroxycholesterol, 7␤-hydroxycholesterol, and 7KC. In contrast to lysates, which efficiently catalyzed both oxidation and reduction, intact cells exclusively reduced 7KC. These findings were confirmed using rat and hamster liver homogenates, intact rat hepatocytes, and intact hamster liver tissue slices. Reduction of 7KC was abolished upon inhibition of 11␤-HSD1 by carbenoxolone (CBX) or 2-hydroxyflavanone. In vivo, after gavage feeding rats, 7KC rapidly appeared in the liver and was converted to 7␤-hydroxycholesterol. CBX significantly decreased the ratio of 7␤-hydroxycholesterol to 7KC, supporting the evidence from cell culture experiments for 11␤-HSD1-dependent reduction of 7KC to 7␤-hydroxycholesterol. Upon inhibition of 11␤-HSD1 by CBX, 7KC tended to accumulate in the liver, and plasma 7KC concentration increased. Together, our results suggest that 11␤-HSD1 efficiently catalyzes the first step in the rapid hepatic metabolism of dietary 7KC, which may explain why dietary 7KC has little or no effect on the development of atherosclerosis.Several in vitro studies demonstrated disturbances of cholesterol metabolism by 7KC 1 (1), including effects on hydroxymethylglutaryl-CoA-reductase and cholesterol 7␣-hydroxylase activities (2), inhibition of cholesterol release from cells (3), and down-regulation of low density lipoprotein receptor expression (4). In addition, 7KC exerts multiple effects by inhibiting nitric oxide release, decreasing glucose permeability, disrupting Ca 2ϩ -flux and inducing apoptosis in vascular cells (1).Oxidized cholesterol metabolites play a potential role in the development of atherosclerosis (1, 5, 6). Among other oxysterols, 7KC is found at micromolar concentrations in human macrophage-foam cells and atherosclerotic lesions. In contrast, plasma 7KC concentrations are in the nanomolar range. The major oxysterols present in atherosclerotic plaques are 27-hydroxycholesterol and 7KC, although the direct role of 7KC in the development and progression of atherosclerosis is still unclear. 27-Hydroxycholesterol is produced by sterol 27-hydroxylase, the first enzyme of the alternative pathway from cholesterol to bile acids in the liver (7). 7KC is believed to be formed non-enzymatically by free radical oxidation of cholesterol (8) or absorbed from dietary intake of processed cholesterol-rich food (9, 10).It was reported that u...

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Section: -Ketocholesterol Reduction By 11␤-hsd1supporting

confidence: 91%

Section: -Ketocholesterol Reduction By 11␤-hsd1mentioning

confidence: 90%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Rapid Hepatic Metabolism of 7-Ketocholesterol by 11β-Hydroxysteroid Dehydrogenase Type 1

Schweizer

Zürcher

Balázs

et al. 2004

Journal of Biological Chemistry

119

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“…7ß-hydroxycholesterol can be metabolized by the enzyme 11ß-hydroxysteroid dehydrogenase type 1 (4). In hamster and chicken microsome preparations, an enzymatic conversion of 7α-hydroxycholesterol into 7-ketocholesterol has been reported (8). It has also been found that ß-amyloid, the toxic peptide in neurons of Alzheimer's disease patients, binds oxysterols and catalyzes its oxidation to 7ß-hydroxycholesterol (9).…”

mentioning

confidence: 98%

Side effects of oxysterols: cytotoxicity, oxidation, inflammation, and phospholipidosis

Véjux

Malvitte

Lizard³

2008

Braz J Med Biol Res

149

132

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11β-Hydroxysteroid dehydrogenase type 1 contributes to the balance between 7-keto- and 7-hydroxy-oxysterols in vivo

Mitić

Shave

Semjonous

et al. 2013

Biochemical Pharmacology

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A comparative study of the conversion of 7-hydroxycholesterol in rabbit, guinea pig, rat, hamster, and chicken

Cited by 15 publications

References 16 publications

Rapid Hepatic Metabolism of 7-Ketocholesterol by 11β-Hydroxysteroid Dehydrogenase Type 1

Rapid Hepatic Metabolism of 7-Ketocholesterol by 11β-Hydroxysteroid Dehydrogenase Type 1

Side effects of oxysterols: cytotoxicity, oxidation, inflammation, and phospholipidosis

11β-Hydroxysteroid dehydrogenase type 1 contributes to the balance between 7-keto- and 7-hydroxy-oxysterols in vivo

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