{"created":"2023-07-27T06:58:26.756546+00:00","id":56863,"links":{},"metadata":{"_buckets":{"deposit":"3b2fcc3b-6b9f-49a8-a0c9-c17aecae2513"},"_deposit":{"created_by":18,"id":"56863","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"56863"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00056863","sets":["2812:2813:2828"]},"author_link":["91550","21551"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2007-12-12","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"3p.","bibliographicVolumeNumber":"2003 – 2005","bibliographic_titles":[{"bibliographic_title":"平成17(2005)年度 科学研究費補助金 基盤研究(C) 研究成果報告書概要"},{"bibliographic_title":"2005 Fiscal Year Final Research Report Summary","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"アストログリアのモデル細胞として培養型C6ラットグリア細胞腫株を用い、このGSHの枯渇下によるアポトーシスの過程で、本研究では不飽和脂肪酸とくにアラキドン酸のアポトーシスに及ぼす影響を調べた。ラットグリア細胞腫はグルタミン酸で細胞内GSHを枯渇誘導すると、細胞内活性酸素が増え、かつ脂質メディエーターであるアラキドン酸からの12-リポオキシゲナーゼ代謝過酸化物を含む脂質のラジカル連鎖反応による過酸化が増大することで細胞膜強度が低下し、同時にアポトーシス関連酵素の失活もしくは減少を来たした。染色体DNAでは、細胞内活性酸素OHラジカルによってグアニン塩基が水酸化反応を受け酸化反応による8-hydroxy-2-deoxyguanosine(8-OH-dG)産生の増加が認められた。一方でDNAの酸化反応を引き起こしながらネクローシス様の細胞死を誘導増進することが明らかになった。\n紫外線による細胞死誘導において、アラキドン酸またはその過酸化物がどのような役割をしているかを、グルタチオン(GSH)枯渇による細胞死誘導の過程で観察された染色体DNAの断片化及び特定の細胞内生理活性物質の変動を調べ、比較検討した。初期段階で活性酸素非依存性の巨大DNA断片化を引き起こし、カスパーゼの活性化を伴うアポトーシスと考えられ、アラキドン酸はDNA断片化を増長させながら紫外線照射による細胞死を促進し、アラキドン酸またはその過酸化物によってその細胞死の一部はNAD,ATPの枯渇を伴うネクローシスに転換されるものと示唆された。これらのGSH枯渇誘導及び紫外線誘導細胞死の実験結果より、グリア細胞腫におけるGSH枯渇誘導での細胞死は、つまり活性酸素関与の場合のその機構はネクローシスであり、活性酸素非依存の場合はアポトーシスによる機構が働くと示唆された。","subitem_description_type":"Abstract"},{"subitem_description":"Glutamate induced glutathione (GSH) depletion leading to cell death in C6 rat glioma cells through accumulation of reactive oxygen species (ROS) or hydroperoxides. A significant increase of 12-lipoxygenase activities was observed in the presence of arachidonic acid (AA) under the GSH depletion. AA promoted the glutamate-induced cell death reducing caspase-3 activity and diminishing internucleosomal DNA fragmentation observed in apoptosis. Furthermore, AA diminished intracellular NAD, ATP and membrane potential revealing a dysfunction of mitochondrial membrane. Ac-DEVD, a caspase inhibitor, did not suppresse the glutamate-induced cytolysis. These results suggest that AA promotes cell death by inducing to necrosis from caspase-3 independent apoptosis through lipid peroxidation initiated by ROS or lipid hydroperoxides generated during the GSH depletion in C6 cells.\nNext, we studied the effect of AA on UV-induced cell death. At lethal dose, UV-C (254 nm) radiation induces cell dysfunction leading to apoptosis or necrosis. During the cell death of T-24 human bladder carcinoma cells, 1-2 Mbp giant DNA fragmentation was observed and consequently the DNA fragmentation was proceeded into high molecular weight 100-800 kbp DNA fragmentation followed by ladder-like inter-nucleosomal DNA fragmentation. Reactive lipid peroxides or oxygen species were not produced. In contrast, increase of caspase-3 and reduction of intracellular NAD and poly (ADP-ribose) polymerase were observed. UV-C radiation induces giant DNA fragmentation leading to apoptosis associated without producing DCFH detectable reactive oxygen species and with activation of caspase-3 and internucleosomal DNA fragmentation in T-24 carcinoma cells.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:15590268, 研究期間(年度):2003 – 2005","subitem_description_type":"Other"},{"subitem_description":"出典：「脂質メディエーターの過酸化を介する神経系細胞死誘導機構の解明」研究成果報告書　課題番号15590268\n（KAKEN：科学研究費助成事業データベース（国立情報学研究所））\n（https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-15590268/155902682005kenkyu_seika_hokoku_gaiyo/)を加工して作成","subitem_description_type":"Other"}]},"item_9_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"金沢大学医学系研究科","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00063137","subitem_identifier_reg_type":"JaLC"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://nrid.nii.ac.jp/ja/search/?kw=10019630"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://nrid.nii.ac.jp/ja/search/?kw=10019630","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-15590268/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-15590268/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-15590268/155902682005kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-15590268/155902682005kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-11-08"}],"displaytype":"detail","filename":"ME-PR-HIGUCHI-Y-kaken 2007-3p.pdf","filesize":[{"value":"110.2 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-HIGUCHI-Y-kaken 2007-3p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/56863/files/ME-PR-HIGUCHI-Y-kaken 2007-3p.pdf"},"version_id":"ff93389e-e96f-486a-8961-e3a53afc4dcd"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"脂質メディエーターの過酸化を介する神経系細胞死誘導機構の解明","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"脂質メディエーターの過酸化を介する神経系細胞死誘導機構の解明"},{"subitem_title":"The study on the glutamate-induced glial cell death mechanism for modulation of apoptosis to necrosis by arachidonic acid-mediated lipid peroxidation","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2828"],"pubdate":{"attribute_name":"公開日","attribute_value":"2021-11-08"},"publish_date":"2021-11-08","publish_status":"0","recid":"56863","relation_version_is_last":true,"title":["脂質メディエーターの過酸化を介する神経系細胞死誘導機構の解明"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:25:16.456139+00:00"}