{"created":"2023-06-19T10:30:14.218918+00:00","id":10462,"links":{},"metadata":{"_buckets":{"deposit":"ab6ad88b-742b-4edc-adc5-7db132230181"},"_deposit":{"created_by":18,"id":"10462","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"10462"},"status":"published"},"_oai":{"id":"oai:muroran-it.repo.nii.ac.jp:00010462","sets":["41:227"]},"author_link":["58532"],"control_number":"10462","item_81_date_granted_17":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2021-03-23"}]},"item_81_degree_grantor_10":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"室蘭工業大学"},{"subitem_degreegrantor_language":"en","subitem_degreegrantor_name":"Muroran Institute of Technology"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"10103","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_81_degree_name_11":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（工学）","subitem_degreename_language":"ja"}]},"item_81_description_25":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_81_description_7":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"アミロイドーシスは、βシートに富むアミロイド原線維の細胞外沈着を特徴とする疾患であり、現在、アミロイド原線維を形成する50種類以上の前駆体タンパク質またはペプチドが知られている。これらが凝集、蓄積しアミロイド原線維としてプラークに沈着することで、臓器機能障害が引き起こされる。アミロイドA（AA）アミロイドーシスは、世界中の人間や家畜に頻繁に見られるアミロイド性疾患であり、関節リウマチや結核など重度の慢性炎症患者に発症する。血清アミロイドA（SAA）は、脊椎動物で高度に進化的に保存された、AAアミロイドーシスにおいて最も重要な前駆体アミロイドタンパク質の1つである。本研究では、まず、AAアミロイドーシスを発症した5つの異なる動物種（マウス、牛、山羊、犬、ラクダ）からアミロイド線維を精製し、これらの線維の幅と交差距離を透過型電子顕微鏡観察により測定した。その結果、精製したアミロイド原線維はクロス構造を持ち、不規則な長さを有する線状の形態を示すことが分かった。また、これらのアミロイド原線維の形態的な特徴は、それぞれの動物間のSAA遺伝子の相同性と相関することが示唆された。本研究ではさらに、アミロイドβ（Aβ）の凝集阻害剤として知られるロスマリン酸（RA）が、in vitroでSAA凝集に対して阻害活性を示すことを、量子ドットナノプローブを用いた微量ハイスループットスクリーニング（MSHTS）システムにより明らかにした。そこで、2% RAを有効成分として含むレモンバーム（Melissa officinalis）抽出物（ME）を食餌によりマウスに投与し、その血液から調製した血清のアミロイド凝集抑制活性と臓器へのSAAの沈着を評価した。興味深いことに、MSHTSシステムで評価したSAAおよびAβ凝集に対するME給餌マウス血清の阻害活性は、対照群よりも高かった。 また、MEを投与したマウス臓器におけるSAA沈着量は、対照群よりも少なく、血清のSAA凝集阻害活性がSAA沈着と関連していることを示唆した。これらの結果は、RAを含むMEの食餌による摂取が血液のアミロイド凝集阻害活性を増強し、臓器におけるSAA沈着を抑制したことを示唆した。さらに、本研究は、MSHTSシステムがin vitroスクリーニングだけでなく、分解され血液に吸収された食品の包括的なアミロイド凝集阻害活性の評価に適用できることを証明した。これらの研究成果は、アミロイド疾患の理解、および治療や予防のための新しい戦略の提供に貢献することが期待される。","subitem_description_language":"ja","subitem_description_type":"Abstract"},{"subitem_description":"Amyloidosis, which is characterized by the extracellular deposit of β-sheet rich amyloid fibrils, is currently classified into more than 50 different types of medical associations based on precursor proteins or peptides. The aggregates of these proteins accumulated and deposited as amyloid fibrils into plaques which resulting organ dysfunction. Amyloid A (AA) amyloidosis is an amyloid-based disease frequently found in humans and livestock worldwide. It develops in patients with severe chronic inflammatory such as rheumatoid arthritis, and tuberculosis, among others. Serum amyloid A (SAA) is a highly evolutionarily conserved protein in vertebrates that is encoded by a family of closely related genes. And it is one of the most important precursor amyloid proteins and plays a vital step in AA amyloidosis. In this study, I first purified amyloid fibrils from five different animal species (mouse, cow, goat, dog, and camel) with AA amyloidosis, and measured these fibrils width and crossover distance by transmission electron microscopy. These results showed that amyloid fibrils had a linear morphology with a cross structure and irregular length in vivo. These data also suggested that the fibrils from different animal species have similar genetic homology in SAA sequences and morphology. Furthermore, I showed that rosmarinic acid (RA), which is a well-known inhibitor of the aggregation of amyloid β (Aβ), displayed inhibitory activity against SAA aggregation in vitro using a microliter-scale high-throughput screening (MSHTS) system with quantum-dot nanoprobes. Therefore, I evaluated the amyloid aggregation inhibitory activity of serum prepared from blood and the deposition of SAA in organs by feeding mice with Melissa officinalis extract (ME) containing 2% RA as an active substance. Interestingly, the inhibitory activity of ME-fed mice sera for SAA and Aβ aggregation, measured with the MSHTS system, were higher than that of the control group. The amount of amyloid deposition in the organs of ME-fed mice was lower than that in the control group, suggesting that the SAA aggregation inhibitory activity of serum is associated with SAA deposition. These results suggested that dietary intake of RA containing ME enhanced amyloid aggregation inhibitory activity of blood and suppressed SAA deposition in organs. Besides, this study also demonstrated that the MSHTS system could be applied to in vitro screening and to monitor the comprehensive activity of metabolized foods adsorbed by blood. I hope these findings will aid in the understanding of amyloid diseases and are inspiring new strategies for therapeutic intervention.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_81_dissertation_number_13":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第476号"}]},"item_81_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.15118/00010401","subitem_identifier_reg_type":"JaLC"}]},"item_81_subject_9":{"attribute_name":"日本十進分類法","attribute_value_mlt":[{"subitem_subject":"499","subitem_subject_scheme":"NDC"}]},"item_81_text_12":{"attribute_name":"学位の種別","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"課程博士"}]},"item_81_text_14":{"attribute_name":"報告番号","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"甲第476号"}]},"item_81_text_15":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"博甲第476号"}]},"item_81_text_16":{"attribute_name":"研究科・専攻","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"工学専攻"}]},"item_81_version_type_24":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorAffiliations":[{"affiliationNameIdentifiers":[],"affiliationNames":[{"affiliationName":""}]}],"creatorNames":[{"creatorName":"LIN, Xuguang","creatorNameLang":"en"},{"creatorName":"リン, シュウグアン","creatorNameLang":"ja"}],"familyNames":[{},{}],"givenNames":[{},{}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-06-23"}],"displaytype":"detail","filename":"A476_summary.pdf","filesize":[{"value":"279.4 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"A476_summary","objectType":"abstract","url":"https://muroran-it.repo.nii.ac.jp/record/10462/files/A476_summary.pdf"},"version_id":"f065e44e-78ea-4f70-aa02-51c90da09e43"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-01-01"}],"displaytype":"simple","filename":"A476.pdf","filesize":[{"value":"14.4 MB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"label":"A476","objectType":"fulltext","url":"https://muroran-it.repo.nii.ac.jp/record/10462/files/A476.pdf"},"version_id":"b55a2c12-6c94-48a6-86d1-d76ab839ca08"}]},"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":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Studies on comparison of AA amyloid fibril morphology in different animal　species and　inhibition of serum amyloid A aggregationby rosmarinic acid","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Studies on comparison of AA amyloid fibril morphology in different animal　species and　inhibition of serum amyloid A aggregationby rosmarinic acid","subitem_title_language":"en"},{"subitem_title":"異なる動物種由来の AA アミロイド線維形態の比較とロスマリン酸による血清アミロイドA凝集の阻害に関する研究","subitem_title_language":"ja"}]},"item_type_id":"81","owner":"18","path":["227"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2021-06-23"},"publish_date":"2021-06-23","publish_status":"0","recid":"10462","relation_version_is_last":true,"title":["Studies on comparison of AA amyloid fibril morphology in different animal　species and　inhibition of serum amyloid A aggregationby rosmarinic acid"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-12-15T03:20:35.409986+00:00"}