{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T08:43:59Z","timestamp":1789461839523,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,3,2]],"date-time":"2015-03-02T00:00:00Z","timestamp":1425254400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 DC009222"],"award-info":[{"award-number":["R01 DC009222"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"crossref","award":["81120108008"],"award-info":[{"award-number":["81120108008"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"crossref","award":["C06 RR014516"],"award-info":[{"award-number":["C06 RR014516"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"crossref","award":["C06 RR015455"],"award-info":[{"award-number":["C06 RR015455"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Our previous work has suggested that traumatic noise activates Rho\u2010<jats:styled-content style=\"fixed-case\">GTP<\/jats:styled-content>ase pathways in cochlear outer hair cells (<jats:styled-content style=\"fixed-case\">OHC<\/jats:styled-content>s), resulting in cell death and noise\u2010induced hearing loss (<jats:styled-content style=\"fixed-case\">NIHL<\/jats:styled-content>). In this study, we investigated Rho effectors, Rho\u2010associated kinases (<jats:styled-content style=\"fixed-case\">ROCK<\/jats:styled-content>s), and the targets of <jats:styled-content style=\"fixed-case\">ROCK<\/jats:styled-content>s, the ezrin\u2010radixin\u2010moesin (<jats:styled-content style=\"fixed-case\">ERM<\/jats:styled-content>) proteins, in the regulation of the cochlear actin cytoskeleton using adult <jats:styled-content style=\"fixed-case\">CBA<\/jats:styled-content>\/J mice under conditions of noise\u2010induced temporary threshold shift (<jats:styled-content style=\"fixed-case\">TTS<\/jats:styled-content>) and permanent threshold shift (<jats:styled-content style=\"fixed-case\">PTS<\/jats:styled-content>) hearing loss, which result in changes to the F\/G\u2010actin ratio. The levels of cochlear <jats:styled-content style=\"fixed-case\">ROCK<\/jats:styled-content>2 and p\u2010<jats:styled-content style=\"fixed-case\">ERM<\/jats:styled-content> decreased 1\u00a0h after either <jats:styled-content style=\"fixed-case\">TTS<\/jats:styled-content>\u2010 or <jats:styled-content style=\"fixed-case\">PTS<\/jats:styled-content>\u2010noise exposure. In contrast, <jats:styled-content style=\"fixed-case\">ROCK<\/jats:styled-content>2 and p\u2010<jats:styled-content style=\"fixed-case\">ERM<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">OHC<\/jats:styled-content>s decreased only after <jats:styled-content style=\"fixed-case\">PTS<\/jats:styled-content>\u2010, not after <jats:styled-content style=\"fixed-case\">TTS<\/jats:styled-content>\u2010noise exposure. Treatment with lysophosphatidic acid, an activator of the Rho pathway, resulted in significant reversal of the F\/G\u2010actin ratio changes caused by noise exposure and attenuated <jats:styled-content style=\"fixed-case\">OHC<\/jats:styled-content> death and <jats:styled-content style=\"fixed-case\">NIHL<\/jats:styled-content>. Conversely, the down\u2010regulation of <jats:styled-content style=\"fixed-case\">ROCK<\/jats:styled-content>2 by pretreatment with <jats:styled-content style=\"fixed-case\">ROCK<\/jats:styled-content>2 si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> reduced the expression of <jats:styled-content style=\"fixed-case\">ROCK<\/jats:styled-content>2 and p\u2010<jats:styled-content style=\"fixed-case\">ERM<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">OHC<\/jats:styled-content>s, exacerbated <jats:styled-content style=\"fixed-case\">TTS<\/jats:styled-content> to <jats:styled-content style=\"fixed-case\">PTS<\/jats:styled-content>, and worsened <jats:styled-content style=\"fixed-case\">OHC<\/jats:styled-content> loss. Additionally, pretreatment with si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> against radixin, an <jats:styled-content style=\"fixed-case\">ERM<\/jats:styled-content> protein, aggravated <jats:styled-content style=\"fixed-case\">TTS<\/jats:styled-content> to <jats:styled-content style=\"fixed-case\">PTS<\/jats:styled-content>. Our results indicate that a <jats:styled-content style=\"fixed-case\">ROCK<\/jats:styled-content>2\u2010mediated <jats:styled-content style=\"fixed-case\">ERM<\/jats:styled-content>\u2010phosphorylation signaling cascade modulates noise\u2010induced hair cell loss and <jats:styled-content style=\"fixed-case\">NIHL<\/jats:styled-content> by targeting the cytoskeleton.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13061-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>We propose the following cascade following noise trauma leading to alteration of the F\u2010actin arrangement in the outer hair cell cytoskeleton: Noise exposure reduces the levels of GTP\u2010RhoA and subsequently diminishes levels of RhoA effector ROCK2 (Rho\u2010associated kinase 2). Phosphorylation of ezrin\u2010radixin\u2010moesin (ERM) by ROCK2 normally allows ERM to cross\u2010link actin filaments with the plasma membrane. Noise\u2010decreased levels of ROCK results in reduction of phosphorylation of ERM that leads to depolymerization of actin filaments. Lysophosphatidic acid (LPA), an agonist of RhoA, binds to the G\u2010protein\u2010coupled receptor (GPCR) leading to activation of RhoA through G\u03b1<jats:sub>12\/13<\/jats:sub> and RhoGEF. Administration of LPA rescues the noise\u2010diminished F\/G\u2010actin ratio.<\/jats:p>","DOI":"10.1111\/jnc.13061","type":"journal-article","created":{"date-parts":[[2015,2,13]],"date-time":"2015-02-13T12:36:41Z","timestamp":1423831001000},"page":"617-628","source":"Crossref","is-referenced-by-count":30,"title":["Noise\u2010induced cochlear F\u2010actin depolymerization is mediated via <scp>ROCK<\/scp>2\/p\u2010<scp>ERM<\/scp> signaling"],"prefix":"10.1111","volume":"133","author":[{"given":"Yu","family":"Han","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Medical University of South Carolina Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianren","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Medical University of South Carolina Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Medical University of South Carolina Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su\u2010Hua","family":"Sha","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Medical University of South Carolina Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,3,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5304.1308"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2000.5046"},{"key":"e_1_2_7_4_1","first-page":"1","article-title":"The role of cleavage of cell structures during apoptosis","volume":"46","author":"Asumendi A.","year":"2000","journal-title":"Cell. 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