論文 - 詳細
| RRC ID | 38466 |
|---|---|
| 著者 | Tomono S, Miyoshi N, Shiokawa H, Iwabuchi T, Aratani Y, Higashi T, Nukaya H, Ohshima H. |
| タイトル | Formation of cholesterol ozonolysis products in vitro and in vivo through a myeloperoxidase-dependent pathway. |
| ジャーナル | J Lipid Res |
| Abstract |
3β-Hydroxy-5-oxo-5,6-secocholestan-6-al (secosterol-A) and its aldolization product 3β-hydroxy-5β-hydroxy-B-norcholestane-6β-carboxaldehyde (secosterol-B) were recently detected in human atherosclerotic tissues and brain specimens, and they may play pivotal roles in the pathogenesis of atherosclerosis and neurodegenerative diseases. However, as their origin remains unidentified, we examined the formation mechanism, the stability, and the fate of secosterols in vitro and in vivo. About 40% of secosterol-A remained unchanged after 3 h incubation in the FBS-free medium, whereas 20% and 40% were converted to its aldehyde-oxidation product, 3β-hydroxy-5-oxo-secocholestan-6-oic acid, and secosterol-B, respectively. In the presence of FBS, almost all secosterol-A was converted immediately to these compounds. Secosterol-B in the medium, with and without FBS, was relatively stable, but ∼30% was converted to its aldehyde-oxidation product, 3β-hydroxy-5β-hydroxy-B-norcholestane-6-oic acid (secoB-COOH). When neutrophil-like differentiated human leukemia HL-60 (nHL-60) cells activated with PMA were cultured in the FBS-free medium containing cholesterol, significantly increased levels of secosterol-A and its aldehyde-oxidation product, but not secosterol-B, were formed. This secosterol-A formation was decreased in the culture of PMA-activated nHL-60 cells containing several reactive oxygen species (ROS) inhibitors and scavengers or in the culture of PMA-activated neutrophils isolated from myeloperoxidase (MPO)-deficient mice. Our results demonstrate that secoterol-A is formed by an ozone-like oxidant generated with PMA-activated neutrophils through the MPO-dependent mechanism. |
| 巻・号 | 52(1) |
| ページ | 87-97 |
| 公開日 | 2011-1-1 |
| DOI | 10.1194/jlr.M006775 |
| PII | S0022-2275(20)40499-7 |
| PMID | 20921334 |
| PMC | PMC2999934 |
| MeSH | Animals Cell Differentiation Cholestanol / analogs & derivatives* Cholestanol / metabolism Cholestanones / metabolism* Cholesterol / metabolism* HL-60 Cells Humans Male Mice Mice, Inbred C57BL Neutrophils / metabolism Norsteroids / metabolism* Oxidation-Reduction Ozone / metabolism* Peroxidase / metabolism* Reactive Oxygen Species / metabolism Secosteroids / metabolism* Signal Transduction |
| IF | 4.483 |
| 引用数 | 27 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Wikipedia |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HL60(RCB0041) |