Disruption of Gap Junction-Mediated Intercellular Communication in the Spiral Ligament Causes Hearing and Outer Hair Cell Loss in the Cochlea of Mice
It is well-known that outer hair cell (OHC) loss occurs in the cochlea of animal models of permanent hearing loss induced by intense noise exposure. Our earlier studies demonstrated the production of hydroxynonenal and peroxynitrite, as well as the disruption of gap junction-mediated intercellular c...
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| Veröffentlicht in: | Biological & pharmaceutical bulletin 2019/01/01, Vol.42(1), pp.73-80 |
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| creator | Nishiyama, Norito Yamaguchi, Taro Yoneyama, Masanori Onaka, Yusuke Ogita, Kiyokazu |
| description | It is well-known that outer hair cell (OHC) loss occurs in the cochlea of animal models of permanent hearing loss induced by intense noise exposure. Our earlier studies demonstrated the production of hydroxynonenal and peroxynitrite, as well as the disruption of gap junction-mediated intercellular communication (GJIC), in the cochlear spiral ligament prior to noise-induced sudden hearing loss. The goal of the present study was to evaluate the mechanism underlying cochlear OHC loss after sudden hearing loss induced by intense noise exposure. In organ of Corti explant cultures from mice, no significant OHC loss was observed after in vitro exposure to 4-hydroxynonenal (a product of lipid peroxidation), H2O2, SIN-1 (peroxynitrite generator), and carbenoxolone (a gap junction inhibitor). Interestingly, in vivo intracochlear carbenoxolone injection through the posterior semicircular canal caused marked OHC and hearing loss, as well as the disruption of gap junction-mediated intercellular communication in the cochlear spiral ligament. However, no significant OHC loss was observed in vivo in animals treated with 4-hydroxynonenal and SIN-1. Taken together, our data suggest that disruption of GJIC in the cochlear lateral wall structures is an important cause of cochlear OHC loss in models of hearing loss, including those induced by noise. |
| doi_str_mv | 10.1248/bpb.b18-00559 |
| format | Article |
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Our earlier studies demonstrated the production of hydroxynonenal and peroxynitrite, as well as the disruption of gap junction-mediated intercellular communication (GJIC), in the cochlear spiral ligament prior to noise-induced sudden hearing loss. The goal of the present study was to evaluate the mechanism underlying cochlear OHC loss after sudden hearing loss induced by intense noise exposure. In organ of Corti explant cultures from mice, no significant OHC loss was observed after in vitro exposure to 4-hydroxynonenal (a product of lipid peroxidation), H2O2, SIN-1 (peroxynitrite generator), and carbenoxolone (a gap junction inhibitor). Interestingly, in vivo intracochlear carbenoxolone injection through the posterior semicircular canal caused marked OHC and hearing loss, as well as the disruption of gap junction-mediated intercellular communication in the cochlear spiral ligament. However, no significant OHC loss was observed in vivo in animals treated with 4-hydroxynonenal and SIN-1. Taken together, our data suggest that disruption of GJIC in the cochlear lateral wall structures is an important cause of cochlear OHC loss in models of hearing loss, including those induced by noise.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.b18-00559</identifier><identifier>PMID: 30606991</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>4-Hydroxynonenal ; Acoustic Stimulation - adverse effects ; Aldehydes - toxicity ; Animal models ; Animals ; carbenoxolone ; Cell Communication - drug effects ; Cell Communication - physiology ; Cell interactions ; Cell signaling ; Cochlea ; Cochlea - drug effects ; Cochlea - metabolism ; Communication ; Disruption ; Exposure ; gap junction-mediated intercellular communication ; Gap Junctions - drug effects ; Gap Junctions - metabolism ; Hair ; Hair Cells, Auditory, Outer - drug effects ; Hair Cells, Auditory, Outer - metabolism ; Hearing loss ; Hearing Loss, Noise-Induced - chemically induced ; Hearing Loss, Noise-Induced - etiology ; Hearing Loss, Noise-Induced - metabolism ; Hearing protection ; Hydrogen peroxide ; Hydrogen Peroxide - toxicity ; Ligaments ; Lipid peroxidation ; Male ; Mice ; Noise ; Noise levels ; noise-induced hearing loss ; Organ Culture Techniques ; Organ of Corti ; outer hair cell loss ; Peroxidation ; Peroxynitrite ; Semicircular canals ; Spiral Ligament of Cochlea - drug effects ; Spiral Ligament of Cochlea - metabolism</subject><ispartof>Biological and Pharmaceutical Bulletin, 2019/01/01, Vol.42(1), pp.73-80</ispartof><rights>2019 The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c658t-914bfbf89c473aed017a9bf8fcfa67a9c005b3a9f279b6d477e2512be5edfba23</citedby><cites>FETCH-LOGICAL-c658t-914bfbf89c473aed017a9bf8fcfa67a9c005b3a9f279b6d477e2512be5edfba23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,1878,4011,27905,27906,27907</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30606991$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nishiyama, Norito</creatorcontrib><creatorcontrib>Yamaguchi, Taro</creatorcontrib><creatorcontrib>Yoneyama, Masanori</creatorcontrib><creatorcontrib>Onaka, Yusuke</creatorcontrib><creatorcontrib>Ogita, Kiyokazu</creatorcontrib><creatorcontrib>Laboratory of Pharmacology</creatorcontrib><creatorcontrib>Faculty of Pharmaceutical Sciences</creatorcontrib><creatorcontrib>Setsunan University</creatorcontrib><title>Disruption of Gap Junction-Mediated Intercellular Communication in the Spiral Ligament Causes Hearing and Outer Hair Cell Loss in the Cochlea of Mice</title><title>Biological & pharmaceutical bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>It is well-known that outer hair cell (OHC) loss occurs in the cochlea of animal models of permanent hearing loss induced by intense noise exposure. Our earlier studies demonstrated the production of hydroxynonenal and peroxynitrite, as well as the disruption of gap junction-mediated intercellular communication (GJIC), in the cochlear spiral ligament prior to noise-induced sudden hearing loss. The goal of the present study was to evaluate the mechanism underlying cochlear OHC loss after sudden hearing loss induced by intense noise exposure. In organ of Corti explant cultures from mice, no significant OHC loss was observed after in vitro exposure to 4-hydroxynonenal (a product of lipid peroxidation), H2O2, SIN-1 (peroxynitrite generator), and carbenoxolone (a gap junction inhibitor). Interestingly, in vivo intracochlear carbenoxolone injection through the posterior semicircular canal caused marked OHC and hearing loss, as well as the disruption of gap junction-mediated intercellular communication in the cochlear spiral ligament. However, no significant OHC loss was observed in vivo in animals treated with 4-hydroxynonenal and SIN-1. Taken together, our data suggest that disruption of GJIC in the cochlear lateral wall structures is an important cause of cochlear OHC loss in models of hearing loss, including those induced by noise.</description><subject>4-Hydroxynonenal</subject><subject>Acoustic Stimulation - adverse effects</subject><subject>Aldehydes - toxicity</subject><subject>Animal models</subject><subject>Animals</subject><subject>carbenoxolone</subject><subject>Cell Communication - drug effects</subject><subject>Cell Communication - physiology</subject><subject>Cell interactions</subject><subject>Cell signaling</subject><subject>Cochlea</subject><subject>Cochlea - drug effects</subject><subject>Cochlea - metabolism</subject><subject>Communication</subject><subject>Disruption</subject><subject>Exposure</subject><subject>gap junction-mediated intercellular communication</subject><subject>Gap Junctions - drug effects</subject><subject>Gap Junctions - metabolism</subject><subject>Hair</subject><subject>Hair Cells, Auditory, Outer - drug effects</subject><subject>Hair Cells, Auditory, Outer - metabolism</subject><subject>Hearing loss</subject><subject>Hearing Loss, Noise-Induced - chemically induced</subject><subject>Hearing Loss, Noise-Induced - etiology</subject><subject>Hearing Loss, Noise-Induced - metabolism</subject><subject>Hearing protection</subject><subject>Hydrogen peroxide</subject><subject>Hydrogen Peroxide - toxicity</subject><subject>Ligaments</subject><subject>Lipid peroxidation</subject><subject>Male</subject><subject>Mice</subject><subject>Noise</subject><subject>Noise levels</subject><subject>noise-induced hearing loss</subject><subject>Organ Culture Techniques</subject><subject>Organ of Corti</subject><subject>outer hair cell loss</subject><subject>Peroxidation</subject><subject>Peroxynitrite</subject><subject>Semicircular canals</subject><subject>Spiral Ligament of Cochlea - drug effects</subject><subject>Spiral Ligament of Cochlea - metabolism</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdUT2P1DAQjRCIOw5KWmSJhiaHP_LlEgXYPbSnK4Dasp3JrleJHeyk4Ifwf5ns3i0SjcejefPmzbwse8voLeNF89FM5tawJqe0LOWz7JqJos5Lzsrn2TWVWKhY2Vxlr1I6UkprysXL7ErQilZSsuvsz2eX4jLNLngSerLRE_m2eLvm-T10Ts_QkTs_Q7QwDMugI2nDOC7eWX1qcp7MByDfJxf1QHZur0fwM2n1kiCRLejo_J5o35GHBVnIVjukQC6yCyk9tbfBHgbQq4R7Z-F19qLXQ4I3j_Em-_n1y492m-8eNnftp11uq7KZc8kK05u-kbaohYaOslpLzHvb6wq_Fo9ihJY9r6WpuqKugZeMGyih643m4ib7cOadYvi1QJrV6NK6qPYQlqQ4qwqGVytX6Pv_oMewRI_qFOcFE0JWZYWo_IyyEbeL0KspulHH34pRtfql0C-FfqmTX4h_98i6mBG6C_rJIARszgCs4smH4Afn4d9sm2rjwhAUp0wiaYFRURyGqgU-DRWc1pxSZGrPTMc06z1cRuk4OzvASVjBFVufi8BL1R50VODFX8bywHY</recordid><startdate>20190101</startdate><enddate>20190101</enddate><creator>Nishiyama, Norito</creator><creator>Yamaguchi, Taro</creator><creator>Yoneyama, Masanori</creator><creator>Onaka, Yusuke</creator><creator>Ogita, Kiyokazu</creator><general>The Pharmaceutical Society of Japan</general><general>Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20190101</creationdate><title>Disruption of Gap Junction-Mediated Intercellular Communication in the Spiral Ligament Causes Hearing and Outer Hair Cell Loss in the Cochlea of Mice</title><author>Nishiyama, Norito ; Yamaguchi, Taro ; Yoneyama, Masanori ; Onaka, Yusuke ; Ogita, Kiyokazu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c658t-914bfbf89c473aed017a9bf8fcfa67a9c005b3a9f279b6d477e2512be5edfba23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>4-Hydroxynonenal</topic><topic>Acoustic Stimulation - adverse effects</topic><topic>Aldehydes - toxicity</topic><topic>Animal models</topic><topic>Animals</topic><topic>carbenoxolone</topic><topic>Cell Communication - drug effects</topic><topic>Cell Communication - physiology</topic><topic>Cell interactions</topic><topic>Cell signaling</topic><topic>Cochlea</topic><topic>Cochlea - drug effects</topic><topic>Cochlea - metabolism</topic><topic>Communication</topic><topic>Disruption</topic><topic>Exposure</topic><topic>gap junction-mediated intercellular communication</topic><topic>Gap Junctions - drug effects</topic><topic>Gap Junctions - metabolism</topic><topic>Hair</topic><topic>Hair Cells, Auditory, Outer - drug effects</topic><topic>Hair Cells, Auditory, Outer - metabolism</topic><topic>Hearing loss</topic><topic>Hearing Loss, Noise-Induced - chemically induced</topic><topic>Hearing Loss, Noise-Induced - etiology</topic><topic>Hearing Loss, Noise-Induced - metabolism</topic><topic>Hearing protection</topic><topic>Hydrogen peroxide</topic><topic>Hydrogen Peroxide - toxicity</topic><topic>Ligaments</topic><topic>Lipid peroxidation</topic><topic>Male</topic><topic>Mice</topic><topic>Noise</topic><topic>Noise levels</topic><topic>noise-induced hearing loss</topic><topic>Organ Culture Techniques</topic><topic>Organ of Corti</topic><topic>outer hair cell loss</topic><topic>Peroxidation</topic><topic>Peroxynitrite</topic><topic>Semicircular canals</topic><topic>Spiral Ligament of Cochlea - drug effects</topic><topic>Spiral Ligament of Cochlea - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nishiyama, Norito</creatorcontrib><creatorcontrib>Yamaguchi, Taro</creatorcontrib><creatorcontrib>Yoneyama, Masanori</creatorcontrib><creatorcontrib>Onaka, Yusuke</creatorcontrib><creatorcontrib>Ogita, Kiyokazu</creatorcontrib><creatorcontrib>Laboratory of Pharmacology</creatorcontrib><creatorcontrib>Faculty of Pharmaceutical Sciences</creatorcontrib><creatorcontrib>Setsunan University</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biological & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nishiyama, Norito</au><au>Yamaguchi, Taro</au><au>Yoneyama, Masanori</au><au>Onaka, Yusuke</au><au>Ogita, Kiyokazu</au><aucorp>Laboratory of Pharmacology</aucorp><aucorp>Faculty of Pharmaceutical Sciences</aucorp><aucorp>Setsunan University</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Disruption of Gap Junction-Mediated Intercellular Communication in the Spiral Ligament Causes Hearing and Outer Hair Cell Loss in the Cochlea of Mice</atitle><jtitle>Biological & pharmaceutical bulletin</jtitle><addtitle>Biol Pharm Bull</addtitle><date>2019-01-01</date><risdate>2019</risdate><volume>42</volume><issue>1</issue><spage>73</spage><epage>80</epage><pages>73-80</pages><issn>0918-6158</issn><eissn>1347-5215</eissn><abstract>It is well-known that outer hair cell (OHC) loss occurs in the cochlea of animal models of permanent hearing loss induced by intense noise exposure. Our earlier studies demonstrated the production of hydroxynonenal and peroxynitrite, as well as the disruption of gap junction-mediated intercellular communication (GJIC), in the cochlear spiral ligament prior to noise-induced sudden hearing loss. The goal of the present study was to evaluate the mechanism underlying cochlear OHC loss after sudden hearing loss induced by intense noise exposure. In organ of Corti explant cultures from mice, no significant OHC loss was observed after in vitro exposure to 4-hydroxynonenal (a product of lipid peroxidation), H2O2, SIN-1 (peroxynitrite generator), and carbenoxolone (a gap junction inhibitor). Interestingly, in vivo intracochlear carbenoxolone injection through the posterior semicircular canal caused marked OHC and hearing loss, as well as the disruption of gap junction-mediated intercellular communication in the cochlear spiral ligament. However, no significant OHC loss was observed in vivo in animals treated with 4-hydroxynonenal and SIN-1. Taken together, our data suggest that disruption of GJIC in the cochlear lateral wall structures is an important cause of cochlear OHC loss in models of hearing loss, including those induced by noise.</abstract><cop>Japan</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>30606991</pmid><doi>10.1248/bpb.b18-00559</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 4-Hydroxynonenal Acoustic Stimulation - adverse effects Aldehydes - toxicity Animal models Animals carbenoxolone Cell Communication - drug effects Cell Communication - physiology Cell interactions Cell signaling Cochlea Cochlea - drug effects Cochlea - metabolism Communication Disruption Exposure gap junction-mediated intercellular communication Gap Junctions - drug effects Gap Junctions - metabolism Hair Hair Cells, Auditory, Outer - drug effects Hair Cells, Auditory, Outer - metabolism Hearing loss Hearing Loss, Noise-Induced - chemically induced Hearing Loss, Noise-Induced - etiology Hearing Loss, Noise-Induced - metabolism Hearing protection Hydrogen peroxide Hydrogen Peroxide - toxicity Ligaments Lipid peroxidation Male Mice Noise Noise levels noise-induced hearing loss Organ Culture Techniques Organ of Corti outer hair cell loss Peroxidation Peroxynitrite Semicircular canals Spiral Ligament of Cochlea - drug effects Spiral Ligament of Cochlea - metabolism |
| title | Disruption of Gap Junction-Mediated Intercellular Communication in the Spiral Ligament Causes Hearing and Outer Hair Cell Loss in the Cochlea of Mice |
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