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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 mg/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-1 alpha), vascular endothelial growth factor (VEGF) and other related proteins were analyzed by Western blot analysis. Immunohistochemical analysis of HIF-1 alpha 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-1 alpha and VEGF protein expression in rat lungs. Concomitant injection of S1P prevented the decrease in the expression of HIF-1 alpha, 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-1 alpha. Concomitant treatment with S1P normalizes the ceramide-S1P balance in the rat lungs and increases HIF-1 alpha protein expression via activation of sphingosine kinase 1; as a consequence, S1P salvages fenretinide induced emphysema in rat lungs."}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Yoshizawa, T", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106272", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Takizawa, S", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106273", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Shimada, S", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106274", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Tokudome, T", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106275", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Shindo, T", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106276", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Matsumoto, K", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106277", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2018-09-13"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "26860551_01.pdf", "filesize": [{"value": "7.7 MB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensefree": "©2016 The Pharmaceutical Society of Japan", "licensetype": "license_note", "mimetype": "application/pdf", "size": 7700000.0, "url": {"label": "26860551_01.pdf", "url": "https://soar-ir.repo.nii.ac.jp/record/20092/files/26860551_01.pdf"}, "version_id": "b34d78cf-d61c-4138-a1d8-3e9e4c36fe20"}]}, "item_keyword": {"attribute_name": "キーワード", "attribute_value_mlt": [{"subitem_subject": "doxorubicin", "subitem_subject_scheme": "Other"}, {"subitem_subject": "adrenomedullin", "subitem_subject_scheme": "Other"}, {"subitem_subject": "heart", "subitem_subject_scheme": "Other"}, {"subitem_subject": "mitochondrion", "subitem_subject_scheme": "Other"}, {"subitem_subject": "survival rate", "subitem_subject_scheme": "Other"}, {"subitem_subject": "cardiac protection", "subitem_subject_scheme": "Other"}]}, "item_language": {"attribute_name": "言語", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"resourcetype": "journal article", "resourceuri": "http://purl.org/coar/resource_type/c_6501"}]}, "item_title": "Effects of Adrenomedullin on Doxorubicin-Induced Cardiac Damage in Mice", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Effects of Adrenomedullin on Doxorubicin-Induced Cardiac Damage in Mice", "subitem_title_language": "en"}]}, "item_type_id": "6", "owner": "1", "path": ["462"], "permalink_uri": "http://hdl.handle.net/10091/00020853", "pubdate": {"attribute_name": "PubDate", "attribute_value": "2018-09-13"}, "publish_date": "2018-09-13", "publish_status": "0", "recid": "20092", "relation": {}, "relation_version_is_last": true, "title": ["Effects of Adrenomedullin on Doxorubicin-Induced Cardiac Damage in Mice"], "weko_shared_id": -1}
Effects of Adrenomedullin on Doxorubicin-Induced Cardiac Damage in Mice
http://hdl.handle.net/10091/00020853
http://hdl.handle.net/10091/00020853434feb45-8284-467f-86c2-07cdcd0c6b0c
名前 / ファイル | ライセンス | アクション |
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26860551_01.pdf (7.7 MB)
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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 | Effects of Adrenomedullin on Doxorubicin-Induced Cardiac Damage in Mice | |||||
言語 | ||||||
言語 | eng | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1248/bpb.b15-00832 | |||||
関連名称 | 10.1248/bpb.b15-00832 | |||||
キーワード | ||||||
主題 | doxorubicin, adrenomedullin, heart, mitochondrion, survival rate, cardiac protection | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_6501 | |||||
タイプ | journal article | |||||
著者 |
Yoshizawa, T
× Yoshizawa, T× Takizawa, S× Shimada, S× Tokudome, T× Shindo, T× Matsumoto, K |
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信州大学研究者総覧へのリンク | ||||||
氏名 | Yoshizawa, Takahiro | |||||
URL | http://soar-rd.shinshu-u.ac.jp/profile/ja.OCyUumkh.html | |||||
出版者 | ||||||
出版者 | PHARMACEUTICAL SOC JAPAN | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Biological and Pharmaceutical Bulletin.39(5):737-746(2015) | |||||
書誌情報 |
Biological and Pharmaceutical Bulletin 巻 39, 号 5, p. 737-746, 発行日 2016-05-01 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Doxorubicin (DOX) is one of the best known anticancer drugs, and is used in the treatment of lymphoma, lung cancer, stomach cancer, and a number of other cancers. However, DOX has some serious side effects, the worst being lethal heart failure. Occasionally, its side effects result in the cessation of the anticancer treatment, thus having a serious adverse influence on prognosis. Agents that can be administered as alternative prophylactics or to ameliorate the side effects of DOX will be useful in increasing the safety and efficacy of anticancer therapy. Adrenomedullin (AM) is a peptide hormone secreted by many organs, including the heart; it has an organ-protective effect, including antiapoptotic, anti-inflammatory, and antioxidative stress. Blood AM levels increase with heart failure; endogenic AM has been suggested in order to protect the heart. Furthermore, exogenous AM administration has shown therapeutic effects for heart failure in patients. However, it is unclear whether AM can protect the heart against drug-induced cardiac injury in vivo. The present study was performed in order to investigate the effects of AM on DOX-induced cardiac damage. Male BALB/c mice were treated with DOX and/or AM. Exogenous AM improved the survival ratio of DOX-treated mice. In addition, AM reduced serum lactate dehydrogenase (LDH) levels following DOX treatment. On pathological examination, AM was shown to inhibit DOX-induced cardiac tissue damage, mitochondrial abnormality, and cell death. These findings suggest that AM has a protective effect against DOX-induced cardiac damage. | |||||
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 | PISSN | |||||
収録物識別子 | 0918-6158 | |||||
書誌レコードID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AA10885497 | |||||
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 | ©2016 The Pharmaceutical Society of Japan | |||||
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=000375169900012 |