{"created":"2023-07-27T06:51:02.276498+00:00","id":44284,"links":{},"metadata":{"_buckets":{"deposit":"ef740863-d5d2-4d8f-9311-431ff5e832dc"},"_deposit":{"created_by":18,"id":"44284","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"44284"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00044284","sets":["2812:2813:2835"]},"author_link":["74734","22000"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"1999-03","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"6p.","bibliographicVolumeNumber":"1997-1998","bibliographic_titles":[{"bibliographic_title":"平成10(1998)年度 科学研究費補助金 基盤研究(C) 研究成果報告書"},{"bibliographic_title":"1998 Fiscal Year Final Research Report","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":"我々は、細胞の増殖・分化・アポトーシスに対する空胞系酸性顆粒の寄与を,bafilomycin A_1の他、プロジギオシン類やデストラキシン等の空胞系プロトンポンプ阻害剤を用いて明らかにするとともに、これら阻害剤のプロトン輸送阻害機構の解明を目指した。\nその結果、(1)デストラキシンBとEは、ともにリソソームのプロトンポンプを阻害し、リソソーム内pHを上昇させたが、PC12細胞の分化誘導作用はデストラキシンEにのみ認められた。(2)プロジギオシン類は、そのH^+/Cl共輸送活性によりプロトンポンプを脱共役する、新規H^+/Cl symporterであることを初めて明らかにすることが出来た。また、(3)bafilomycin A_1同様、ブロジギオシン類も神経突起伸展(NOG)を誘導することを発見した。(4)そこで、両プロトンポンプ阻害剤によるNOG誘導作用の特徴を検討したところ、ともに新たなRNA及び蛋白質合成を必要とし、MAPキナーゼ、セリン・スレオニンホスファターゼ、チロシンキナーゼ、チロシンホスファターゼ、カルモジュリン、ホスフォリパーゼA_2依存性であるが、trkチロシンキナーゼやAキナーゼには非依存性である等、両情報伝達経路は酷似していることが判明した。(5)また、tambjamineグループのBE-18591もH^+/Cl symporter活性を示し、免疫抑制や、NOG・アボトーシス誘導作用を示すことを見い出した。(6)ところが、同じH^+/Cl symporterでも、tetrapyrroleは増殖阻害・細胞死誘導作用はあるがNOG作用は示さなかった。\n以上の結果より、pH変化やプロトンポンプ活性自身は、少なくともNOG誘導の直接の引き金にはなっていないと結論した。","subitem_description_type":"Abstract"},{"subitem_description":"In this research project, we have studied the machanism of (1) inhibition of cell growth, (2) induction of cell differentiation, and (3) induction of apoptosis, by V-ATPase inhibitors like bafilomycins, prodigiosins and destruxins, as well as the mechanims of inhibition of proton translocation by these inhibitors.\nWe found (1) that both destrauxin-B and -E inhibited lysosomal proton pump, but only destruxin-E induced induced neurite out growth (NOG) of PC12 cells., (2) that prodigisins uncoupled various proton pump activities due to their H ^+ /Cl symport activity, (3) that prodigiosins, like bafilomycin A ^<1'> induced neurite out growth (NOG), and (4) that the prodigiosin-induced NOG, like bafolomycin-induced one, required de novo synthesis of new messenger RNA as well as protein synthesis, was sensitive to the inhibitors of MAP kinases, serine/threonine phosphatases, tyr-kinases, tyr-phosphatases, calmidulin and phospholipase A ^<2' > but resistant to inhibitors of trk tyrosine kinase and protein kinase A.BE-18591, a tambjamine group antibiotics, also behaved as H ^+ /CU symporters and inhibited hog gastric proton pump, inhibit *cid secretion by gastric parietal cells, inhibited osteoclast differentiation, suppressed proliferation of immune lymphocytes, and induced both NOG and apoptosis, suggesting that the variety of biological activities displayed by these H ^+ /C1 symporters may be due to their H ^+ /C1 symport activity. However, tetrapyrrole, another H ^+ /CV symporter, did not induced NOG.\nFrom these results, we conclud that the effect of V-ATPase inhibitors on the intracellular pH does not participate in the variety of biological activities (including induction of NOG) displayed by these compounds.","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:09672220, 研究期間(年度):1997-1998","subitem_description_type":"Other"},{"subitem_description":"出典：「V-ATPase 阻害剤による分化・細胞死誘導機構」研究成果報告書　課題番号09672220\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　　　本文データは著者版報告書より作成","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00050626","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"金沢大学薬学部"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/search/?qm=10119563"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=10119563","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672220/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672220/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-09672220/096722201998kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-09672220/096722201998kenkyu_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":"2018-04-26"}],"displaytype":"detail","filename":"PH-PR-OHKUMA-S-kaken 1999-6p.pdf","filesize":[{"value":"284.9 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"PH-PR-OHKUMA-S-kaken 1999-6p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/44284/files/PH-PR-OHKUMA-S-kaken 1999-6p.pdf"},"version_id":"013149a1-b471-4b90-b516-a2fec524391e"}]},"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":"V-ATPase 阻害剤による分化・細胞死誘導機構","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"V-ATPase 阻害剤による分化・細胞死誘導機構"},{"subitem_title":"Mechanism of induction of cell differentiation and cell death by inhibitors against V-ATPase","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2835"],"pubdate":{"attribute_name":"公開日","attribute_value":"2018-04-26"},"publish_date":"2018-04-26","publish_status":"0","recid":"44284","relation_version_is_last":true,"title":["V-ATPase 阻害剤による分化・細胞死誘導機構"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:49:11.069833+00:00"}