{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T04:11:38Z","timestamp":1793765498522,"version":"4.6.1"},"reference-count":54,"publisher":"SAGE Publications","issue":"15","license":[{"start":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T00:00:00Z","timestamp":1430438400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Aims:<\/jats:italic>\n                    <\/jats:bold>\n                    Reactive oxygen species play a dual role in mediating both cell stress and defense pathways. Here, we used pharmacological manipulations and siRNA silencing to investigate the relationship between autophagy and oxidative stress under conditions of noise-induced temporary, permanent, and severe permanent auditory threshold shifts (temporary threshold shift [TTS], permanent threshold shift [PTS], and severe PTS [sPTS], respectively) in adult CBA\/J mice.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Results:<\/jats:italic>\n                    <\/jats:bold>\n                    Levels of oxidative stress markers (4-hydroxynonenal [4-HNE] and 3-nitrotyrosine [3-NT]) increased in outer hair cells (OHCs) in a noise-dose-dependent manner, whereas levels of the autophagy marker microtubule-associated protein light chain 3 B (LC3B) were sharply elevated after TTS but rose only slightly in response to PTS and were unaltered by sPTS noise. Furthermore, green fluorescent protein (GFP) intensity increased in GFP-LC3 mice after TTS-noise exposure. Treatment with rapamycin, an autophagy activator, significantly increased LC3B expression, while diminishing 4-HNE and 3-NT levels, reducing noise-induced hair cell loss, and, subsequently, noise-induced hearing loss (NIHL). In contrast, treatment with either the autophagy inhibitor 3-methyladenine (3MA) or LC3B siRNA reduced LC3B expression, increased 3-NT and 4-HNE levels, and exacerbated TTS to PTS.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Innovation:<\/jats:italic>\n                    <\/jats:bold>\n                    This study demonstrates a relationship between oxidative stress and autophagy in OHCs and reveals that autophagy is an intrinsic cellular process that protects against NIHL by attenuating oxidative stress.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Conclusions:<\/jats:italic>\n                    <\/jats:bold>\n                    The results suggest that the lower levels of oxidative stress incurred by TTS-noise exposure induce autophagy, which promotes OHC survival. However, excessive oxidative stress under sPTS-noise conditions overwhelms the beneficial potential of autophagy in OHCs and leads to OHC death and NIHL.\n                    <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                    22, 1308\u20131324.\n                  <\/jats:p>","DOI":"10.1089\/ars.2014.6004","type":"journal-article","created":{"date-parts":[[2015,2,19]],"date-time":"2015-02-19T05:22:21Z","timestamp":1424323341000},"page":"1308-1324","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":155,"title":["Autophagy Attenuates Noise-Induced Hearing Loss by Reducing Oxidative Stress"],"prefix":"10.1177","volume":"22","author":[{"given":"Hu","family":"Yuan","sequence":"first","affiliation":[{"name":"Medical University of South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianren","family":"Wang","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla","family":"Hill","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Lemasters","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Ming","family":"Yang","sequence":"additional","affiliation":[{"name":"Chinese PLA General Hospital","place":["People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Hua","family":"Sha","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2015,5,20]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.2694"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-7-83"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(87)90129-8"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.3.1025-1040.2005"},{"key":"e_1_3_3_6_2","first-page":"3065","article-title":"Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer","volume":"118","author":"Carracedo A","year":"2008","unstructured":"Carracedo A, , Ma L, , Teruya-Feldstein J, , Rojo F, , Salmena L, , Alimonti A, , Egia A, , Sasaki AT, , Thomas G, , Kozma SC, , Papa A, , Nardella C, , Cantley LC, , Baselga J, , and Pandolfi PP. Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. 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Excitotoxicity and plasticity of IHC-auditory nerve contributes to both temporary and permanent threshold shift. In: Scientific Basis of Noise-induced Hearing Loss, edited by Axelsson A, , Borchgrevink HM, , Hamernik RP, , Hellstr\u00f6m PA, , Henderson D, , and Salvi RJ. 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