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Fenretinide Causes Emphysema, Which Is Prevented by Sphingosine 1-Phoshate
http://hdl.handle.net/10091/00020854
http://hdl.handle.net/10091/00020854def10baf-5858-4432-8bd3-9e63a5c13e9d
名前 / ファイル | ライセンス | アクション |
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24591127_01.pdf (813.2 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2018-09-13 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Fenretinide Causes Emphysema, Which Is Prevented by Sphingosine 1-Phoshate | |||||
言語 | ||||||
言語 | eng | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1371/journal.pone.0053927 | |||||
関連名称 | 10.1371/journal.pone.0053927 | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_6501 | |||||
タイプ | journal article | |||||
著者 |
Yasuo, M
× Yasuo, M× Mizuno, S× Allegood, J× Kraskauskas, D× Bogaard, HJ× Spiegel, S× Voelkel, NF |
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信州大学研究者総覧へのリンク | ||||||
氏名 | Yasuo, Masanori | |||||
URL | https://soar-rd.shinshu-u.ac.jp/profile/ja.ypnegpkh.html | |||||
出版者 | ||||||
出版者 | PUBLIC LIBRARY SCIENCE | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | PLOS ONE.8(1):e53927(2013) | |||||
書誌情報 |
PLOS ONE 巻 8, 号 1, p. e53927, 発行日 2013-01-11 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Sphingolipids play a role in the development of emphysema and ceramide levels are increased in experimental models of emphysema; however, the mechanisms of ceramide-related pulmonary emphysema are not fully understood. Here we examine mechanisms of ceramide-induced pulmonary emphysema. Male Sprague-Dawley rats were treated with fenretinide (20 mg/kg BW), a synthetic derivative of retinoic acid that causes the formation of ceramide, and we postulated that the effects of fenretinide could be offset by administering sphingosine 1-phosphate (S1P) (100 µg/kg BW). Lung tissues were analyzed and mean alveolar airspace area, total length of the alveolar perimeter and the number of caspase-3 positive cells were measured. Hypoxia-inducible factor alpha (HIF-1α), vascular endothelial growth factor (VEGF) and other related proteins were analyzed by Western blot analysis. Immunohistochemical analysis of HIF-1α was also performed. Ceramide, dihydroceramide, S1P, and dihydro-S1P were measured by mass spectrometer. Chronic intraperitoneal injection of fenretinide increased the alveolar airspace surface area and increased the number of caspase-3 positive cells in rat lungs. Fenretinide also suppressed HIF-1α and VEGF protein expression in rat lungs. Concomitant injection of S1P prevented the decrease in the expression of HIF-1α, VEGF, histone deacetylase 2 (HDAC2), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein expression in the lungs. S1P injection also increased phosphorylated sphingosine kinase 1. Dihydroceramide was significantly increased by fenretinide injection and S1P treatment prevented the increase in dihydroceramide levels in rat lungs. These data support the concept that increased de novo ceramide production causes alveolar septal cell apoptosis and causes emphysema via suppressing HIF-1α. Concomitant treatment with S1P normalizes the ceramide-S1P balance in the rat lungs and increases HIF-1α protein expression via activation of sphingosine kinase 1; as a consequence, S1P salvages fenretinide induced emphysema in rat lungs. | |||||
資源タイプ(コンテンツの種類) | ||||||
内容記述タイプ | Other | |||||
内容記述 | Article | |||||
ISSN | ||||||
収録物識別子タイプ | EISSN | |||||
収録物識別子 | 1932-6203 | |||||
PubMed | ||||||
識別子タイプ | PMID | |||||
関連識別子 | https://www.ncbi.nlm.nih.gov/pubmed/23326540 | |||||
関連名称 | 23326540 | |||||
権利 | ||||||
権利情報 | © 2013 Yasuo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | |||||
出版タイプ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
WoS | ||||||
表示名 | Web of Science | |||||
URL | http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000314705800089 |