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Sibutramine facilitates apoptosis and contraction of aortic smooth muscle cells through elevating production of reactive oxygen species.
https://gifu-pu.repo.nii.ac.jp/records/13468
https://gifu-pu.repo.nii.ac.jp/records/1346838167dcd-3dee-48ea-98df-16d703fc8ec7
| Item type | 研究室原著論文(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-03-05 | |||||
| タイトル | ||||||
| タイトル | Sibutramine facilitates apoptosis and contraction of aortic smooth muscle cells through elevating production of reactive oxygen species. | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Aorta | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Apoptosis | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Cyclobutanes | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Humans | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Muscle, Smooth, Vascular | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Nitric Oxide | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Reactive Oxygen Species | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| item_3_textarea_2 | ||||||
| 値 | Sibutramine had been prescribed as an oral anorexiant that reduces dietary intake, but was withdrawn from the market due to frequent occurrence of severe cardiovascular events including hypertension. To elucidate the pathogenic mechanism of hypertension, we here investigated whether sibutramine facilitates damage and contraction of human aortic smooth muscle (HASM) cells or not. Treatment with sibutramine provoked HASM cell apoptosis, which was attributed to production of reactive oxygen species and mitochondria dysfunction. In addition, the drug treatment of the cell promoted calcium influx, phosphorylation of myosin light chain and contraction, which were abrogated by pretreating the cells with antioxidant and nitric oxide (NO) donor. Thus, the drug-evoked contraction is likely due to a preceding disturbance of balance between the drug-elicited reactive oxygen species production and exogenous NO supply. Compared to sibutramine, its N-desmethyl and N-didesmethyl metabolites exhibited much less toxicity and contraction against HASM cells, in which sibutramine was hardly demethylated. The low metabolic capacity of the cells may also be pertinent to the damage and contraction elicited by sibutramine. Taken together, our data suggest that sibutramine facilitates apoptosis and contraction of aortic smooth muscle cells through elevating production of reactive oxygen species and decreasing exogenous NO supply, leading to pathogenesis of hypertension. | |||||
| bibliographic_information |
en : European journal of pharmacology 巻 841, 号 -, p. 113-121, ページ数 9, 発行日 2018-12-15 |
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| item_3_text_4 | ||||||
| 値 | 10.1016/j.ejphar.2018.10.009. | |||||
