{"created":"2023-06-20T13:21:05.720293+00:00","id":1188,"links":{},"metadata":{"_buckets":{"deposit":"a9c80dcc-761e-4044-80cc-5b5a2edd9618"},"_deposit":{"created_by":1,"id":"1188","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"1188"},"status":"published"},"_oai":{"id":"oai:ir.soken.ac.jp:00001188","sets":["2:430:22"]},"author_link":["0","0","0"],"item_1_creator_2":{"attribute_name":"著者名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"東, 智広"}],"nameIdentifiers":[{}]}]},"item_1_creator_3":{"attribute_name":"フリガナ","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"ヒガシ, トモヒロ"}],"nameIdentifiers":[{}]}]},"item_1_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2007-03-23"}]},"item_1_degree_grantor_5":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"総合研究大学院大学"}]}]},"item_1_degree_name_6":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（理学）"}]},"item_1_description_12":{"attribute_name":"要旨","attribute_value_mlt":[{"subitem_description":"TRP (transient receptor potential) channels were first described in <i>Drosophila</i>, where photoreceptors carrying <i>trp</i> gene mutations exhibited an abnormal transient responsiveness to continuous light. In mammals, TRP channels comprise six related protein families (TRPC, TRPV,TRPM,TRPA,TRPML,TRPP). In genera1, TRP channels are ubiquitously expressed, indicating that most ce11s have a number of TRP channel proteins. Of these channels, I focused on TRPV1 and TRPV4 functions. In chapter 1, I investigated the functional interaction of TRPVI with inflammatory mediators, prostaglandins. Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) and prostaglandin I<sub>2</sub> (PGI<sub>2</sub>) are major inflammatory mediators that play important roles in pain sensation and hyperalgesia. The role of their receptors (EP and IP, respectively) in inflammation has been well documented, although the EP receptor subtypes involved in this process and the underlying cellular mechanisms remain to be elucidated. <br />The capsaicin receptor TRPV1 is a nonselective cation channel expressed in sensory neurons and activated by various noxious stimuli. TRPV1 has been reported to be critica1 for inflammatory pain mediated through PKA- and PKC-dependent pathways. PGE<sub>2</sub> or PGI<sub>2</sub> increased or sensitized TRPV1 responses through EP<sub>1</sub> or IP receptors, respectively predominantly in a PKC-dependent manner in both HEK293 cells expressing TRPV1 and mouse DRG neurons. In the presence of PGE<sub>2</sub> or PGI<sub>2</sub>, the temperature threshold for TRPV 1 activation was reduced below 35℃, so that temperatures near body temperature are sufficient to activate TRPV1. A PKA-dependent pathway was also involved in the potentiation of TRPV1 through EP<sub>4</sub> and IP receptors upon exposure to PGE<sub>2</sub> and PGI<sub>2</sub>, respectively. Both  PGE<sub>2</sub>-induced thermal hyperalgesia and inflammatory nociceptive responses were diminished in TRPV 1-deficient mice and EP１-deficient mice. IP receptor involvement was also demonstrated using TRPV1-deficient mice and IP-deficient mice. Thus, the potentiation or sensitization of TRPV1 activity through EP1 or IP activation might be one important  mechanism underlying the peripheral nociceptive actions of PGE<sub>2</sub> or PGI<sub>2</sub>.<br />　　　In chapter 2, I examined the interaction of TRPV4 with its binding protein. TRPV4, a member of TRPV subfamily, is a nonselective cation channel that is activated by hypotonic stimulus, warm temperatures (～25-34℃) or chemica1 compounds such as 4α-PDD, and is  expressed in various tissues. To investigate TRPV4 function, I screened a cDNA library from keratinocytes to identify TRPV4 interacting proteins using a yeast two-hybrid system. Sequence analysis revealed that one of the positive clones partially encodes ENH (Enigma Homologue). He found that the N terminal region of TRPV4 bound to LIM domains of ENH.<br /> When both TRPV4 and ENH were co-expressed in HEK293 cells, patch-clamp analyses showed that 4α-PDD-evoked currents were larger than those observed in cells expressing TRPV4 alone.However, the increase in the 4α-PDD-evoked currents was prevented by a PMA treatment in the ce11s expressing TRPV4 with ENH. PKCε was found to be involved in the process and ENH was phopshorylated by PKC activation. These results indicate that ENH regulates TRPV4 upon their physical association depending on PKC activity.","subitem_description_type":"Other"}]},"item_1_description_7":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_description":"総研大甲第1074号","subitem_description_type":"Other"}]},"item_1_select_14":{"attribute_name":"所蔵","attribute_value_mlt":[{"subitem_select_item":"有"}]},"item_1_select_8":{"attribute_name":"研究科","attribute_value_mlt":[{"subitem_select_item":"生命科学研究科"}]},"item_1_select_9":{"attribute_name":"専攻","attribute_value_mlt":[{"subitem_select_item":"20 生理科学専攻"}]},"item_1_text_10":{"attribute_name":"学位授与年度","attribute_value_mlt":[{"subitem_text_value":"2006"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"HIGASHI, Tomohiro","creatorNameLang":"en"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-02-17"}],"displaytype":"simple","filename":"甲1074_要旨.pdf","filesize":[{"value":"240.1 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"要旨・審査要旨","url":"https://ir.soken.ac.jp/record/1188/files/甲1074_要旨.pdf"},"version_id":"34224a9c-d8e7-4f2a-9352-35c27bf0d694"}]},"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":"thesis","resourceuri":"http://purl.org/coar/resource_type/c_46ec"}]},"item_title":"Regulation Mechanisms of TRPV Channels by Protein Kinase C","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Regulation Mechanisms of TRPV Channels by Protein Kinase C"},{"subitem_title":"Regulation Mechanisms of TRPV Channels by Protein Kinase C","subitem_title_language":"en"}]},"item_type_id":"1","owner":"1","path":["22"],"pubdate":{"attribute_name":"公開日","attribute_value":"2010-02-22"},"publish_date":"2010-02-22","publish_status":"0","recid":"1188","relation_version_is_last":true,"title":["Regulation Mechanisms of TRPV Channels by Protein Kinase C"],"weko_creator_id":"1","weko_shared_id":1},"updated":"2023-06-20T15:55:39.687214+00:00"}