Ethylbenzene induces hearing loss by triggering mitochondrial impairments and excess apoptosis in cochlear progenitor cells via suppressing the Wnt/β-catenin signaling
Ethylbenzene (EB) is widely distributed at low levels in the environment from vehicle emissions, industrial discharge, cigarette smoke, and in some food and consumer products. Evidence shows that EB exposure is associated with hearing loss, yet the mechanisms are unclear. This study aimed to explore...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651323002257 |
| _version_ | 1811159989134295040 |
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| author | Ming Zhang Tengjiao Qu Siyu Liu Fangjin Yu Lin Fan Dafeng Lin Qiang Zhang Fangfang Song Meibian Zhang Bo Cui Shun Zhang |
| author_facet | Ming Zhang Tengjiao Qu Siyu Liu Fangjin Yu Lin Fan Dafeng Lin Qiang Zhang Fangfang Song Meibian Zhang Bo Cui Shun Zhang |
| author_sort | Ming Zhang |
| collection | DOAJ |
| description | Ethylbenzene (EB) is widely distributed at low levels in the environment from vehicle emissions, industrial discharge, cigarette smoke, and in some food and consumer products. Evidence shows that EB exposure is associated with hearing loss, yet the mechanisms are unclear. This study aimed to explore the role of the Wnt/β-catenin signaling pathway, which plays a key role during cochlear development, in EB-induced hearing loss. In vitro, we found that EB treatment decreased the viability of cochlear progenitor cells (CPCs), isolated from the cochleae of neonatal rats and crucial for cochlear hair cells generation and hearing construction, via inducing mitochondrial impairments and excessive apoptosis. These were accompanied by the inactivation of the Wnt/β-catenin signaling cascade, as manifested by the decreased levels of related molecules β-catenin, LEF-1 and Lgr5. These findings were further confirmed by knocking down β-catenin and immunofluorescence analysis. Interestingly, adenovirus-mediated β-catenin overexpression activated the Wnt/β-catenin signaling network, alleviated mitochondrial impairments, reduced cell apoptosis, therefore promoting CPCs survival under EB treatment conditions. Finally, using adult Sprague–Dawley rats as an in vivo model with EB inhalation for 13 weeks, we found that exposure to EB decreased body weight gain, increased the hearing thresholds at different exposure stages, along with Wnt/β-catenin signaling pathway suppression in cochlear tissue. More importantly, cochlear microinjection of recombinant lentivirus expressing β-catenin significantly reversed EB-elicited these deleterious effects. Collectively, our results indicate that EB induces hearing loss by triggering mitochondrial impairments and excess apoptosis in CPCs via suppressing the Wnt/β-catenin signaling, and provide clues for the possible therapy. |
| first_indexed | 2024-04-10T05:50:05Z |
| format | Article |
| id | doaj.art-cbefee918b204e4486de85044ff8593c |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-10T05:50:05Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-cbefee918b204e4486de85044ff8593c2023-03-05T04:23:06ZengElsevierEcotoxicology and Environmental Safety0147-65132023-04-01254114721Ethylbenzene induces hearing loss by triggering mitochondrial impairments and excess apoptosis in cochlear progenitor cells via suppressing the Wnt/β-catenin signalingMing Zhang0Tengjiao Qu1Siyu Liu2Fangjin Yu3Lin Fan4Dafeng Lin5Qiang Zhang6Fangfang Song7Meibian Zhang8Bo Cui9Shun Zhang10Department of Occupational Health Comprehensive Management, Shenzhen Prevention and Treatment Center for Occupational Diseases, Shenzhen 518020, ChinaDepartment of Occupational and Environmental Health, MOE Key Laboratory of Environment and Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaSchool of Public Health, Tianjin Medical University, Tianjin 300070, ChinaDepartment of Occupational and Environmental Health, MOE Key Laboratory of Environment and Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaSchool of Public Health, Tianjin Medical University, Tianjin 300070, ChinaDepartment of Occupational Health Comprehensive Management, Shenzhen Prevention and Treatment Center for Occupational Diseases, Shenzhen 518020, ChinaSchool of Public Health, Tianjin Medical University, Tianjin 300070, ChinaDepartment of Epidemiology and Biostatistics, Tianjin Key Laboratory of Molecular Cancer Epidemiology, Tianjin Key Laboratory of Cancer Prevention and Therapy, MOE Key Laboratory of Breast Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, ChinaNational Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, ChinaTianjin Institute of Environmental and Operational Medicine, Tianjin 300050, China; Corresponding authors.Department of Occupational and Environmental Health, MOE Key Laboratory of Environment and Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Corresponding authors.Ethylbenzene (EB) is widely distributed at low levels in the environment from vehicle emissions, industrial discharge, cigarette smoke, and in some food and consumer products. Evidence shows that EB exposure is associated with hearing loss, yet the mechanisms are unclear. This study aimed to explore the role of the Wnt/β-catenin signaling pathway, which plays a key role during cochlear development, in EB-induced hearing loss. In vitro, we found that EB treatment decreased the viability of cochlear progenitor cells (CPCs), isolated from the cochleae of neonatal rats and crucial for cochlear hair cells generation and hearing construction, via inducing mitochondrial impairments and excessive apoptosis. These were accompanied by the inactivation of the Wnt/β-catenin signaling cascade, as manifested by the decreased levels of related molecules β-catenin, LEF-1 and Lgr5. These findings were further confirmed by knocking down β-catenin and immunofluorescence analysis. Interestingly, adenovirus-mediated β-catenin overexpression activated the Wnt/β-catenin signaling network, alleviated mitochondrial impairments, reduced cell apoptosis, therefore promoting CPCs survival under EB treatment conditions. Finally, using adult Sprague–Dawley rats as an in vivo model with EB inhalation for 13 weeks, we found that exposure to EB decreased body weight gain, increased the hearing thresholds at different exposure stages, along with Wnt/β-catenin signaling pathway suppression in cochlear tissue. More importantly, cochlear microinjection of recombinant lentivirus expressing β-catenin significantly reversed EB-elicited these deleterious effects. Collectively, our results indicate that EB induces hearing loss by triggering mitochondrial impairments and excess apoptosis in CPCs via suppressing the Wnt/β-catenin signaling, and provide clues for the possible therapy.http://www.sciencedirect.com/science/article/pii/S0147651323002257EthylbenzeneHearing lossWnt/β-cateninCochlear progenitor cellsMitochondrial impairments |
| spellingShingle | Ming Zhang Tengjiao Qu Siyu Liu Fangjin Yu Lin Fan Dafeng Lin Qiang Zhang Fangfang Song Meibian Zhang Bo Cui Shun Zhang Ethylbenzene induces hearing loss by triggering mitochondrial impairments and excess apoptosis in cochlear progenitor cells via suppressing the Wnt/β-catenin signaling Ecotoxicology and Environmental Safety Ethylbenzene Hearing loss Wnt/β-catenin Cochlear progenitor cells Mitochondrial impairments |
| title | Ethylbenzene induces hearing loss by triggering mitochondrial impairments and excess apoptosis in cochlear progenitor cells via suppressing the Wnt/β-catenin signaling |
| title_full | Ethylbenzene induces hearing loss by triggering mitochondrial impairments and excess apoptosis in cochlear progenitor cells via suppressing the Wnt/β-catenin signaling |
| title_fullStr | Ethylbenzene induces hearing loss by triggering mitochondrial impairments and excess apoptosis in cochlear progenitor cells via suppressing the Wnt/β-catenin signaling |
| title_full_unstemmed | Ethylbenzene induces hearing loss by triggering mitochondrial impairments and excess apoptosis in cochlear progenitor cells via suppressing the Wnt/β-catenin signaling |
| title_short | Ethylbenzene induces hearing loss by triggering mitochondrial impairments and excess apoptosis in cochlear progenitor cells via suppressing the Wnt/β-catenin signaling |
| title_sort | ethylbenzene induces hearing loss by triggering mitochondrial impairments and excess apoptosis in cochlear progenitor cells via suppressing the wnt β catenin signaling |
| topic | Ethylbenzene Hearing loss Wnt/β-catenin Cochlear progenitor cells Mitochondrial impairments |
| url | http://www.sciencedirect.com/science/article/pii/S0147651323002257 |
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