Involvement of Cholesterol Metabolic Pathways in Recovery from Noise-Induced Hearing Loss
The objective of this study was to explore the molecular mechanisms of acute noise-induced hearing loss and recovery of steady-state noise-induced hearing loss using miniature pigs. We used miniature pigs exposed to white noise at 120 dB (A) as a model. Auditory brainstem response (ABR) measurements...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2020/6235948 |
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| author | Na Sai Xi Shi Yan Zhang Qing-qing Jiang Fei Ji Shuo-long Yuan Wei Sun Wei-Wei Guo Shi-Ming Yang Wei-Ju Han |
| author_facet | Na Sai Xi Shi Yan Zhang Qing-qing Jiang Fei Ji Shuo-long Yuan Wei Sun Wei-Wei Guo Shi-Ming Yang Wei-Ju Han |
| author_sort | Na Sai |
| collection | DOAJ |
| description | The objective of this study was to explore the molecular mechanisms of acute noise-induced hearing loss and recovery of steady-state noise-induced hearing loss using miniature pigs. We used miniature pigs exposed to white noise at 120 dB (A) as a model. Auditory brainstem response (ABR) measurements were made before noise exposure, 1 day and 7 days after noise exposure. Proteomic Isobaric Tags for Relative and Absolute Quantification (iTRAQ) was used to observe changes in proteins of the miniature pig inner ear following noise exposure. Western blot and immunofluorescence were performed for further quantitative and qualitative analysis of proteomic changes. The average ABR-click threshold of miniature pigs before noise exposure, 1 day and 7 days after noise exposure, were 39.4 dB SPL, 67.1 dB SPL, and 50.8 dB SPL, respectively. In total, 2,158 proteins were identified using iTRAQ. Both gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) database analyses showed that immune and metabolic pathways were prominently involved during the impairment stage of acute hearing loss. During the recovery stage of acute hearing loss, most differentially expressed proteins were related to cholesterol metabolism. Western blot and immunofluorescence showed accumulation of reactive oxygen species and nuclear translocation of NF-κB (p65) in the hair cells of miniature pig inner ears during the acute hearing loss stage after noise exposure. Nuclear translocation of NF-κB (p65) may be associated with overexpression of downstream inflammatory factors. Apolipoprotein (Apo) A1 and Apo E were significantly upregulated during the recovery stage of hearing loss and may be related to activation of cholesterol metabolic pathways. This is the first study to use proteomics analysis to analyze the molecular mechanisms of acute noise-induced hearing loss and its recovery in a large animal model (miniature pigs). Our results showed that activation of metabolic, inflammatory, and innate immunity pathways may be involved in acute noise-induced hearing loss, while cholesterol metabolic pathways may play an important role in recovery of hearing ability following noise-induced hearing loss. |
| format | Article |
| id | doaj-art-558cec6a30964306a9be40c66136dcfd |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-558cec6a30964306a9be40c66136dcfd2025-02-03T00:58:44ZengWileyNeural Plasticity2090-59041687-54432020-01-01202010.1155/2020/62359486235948Involvement of Cholesterol Metabolic Pathways in Recovery from Noise-Induced Hearing LossNa Sai0Xi Shi1Yan Zhang2Qing-qing Jiang3Fei Ji4Shuo-long Yuan5Wei Sun6Wei-Wei Guo7Shi-Ming Yang8Wei-Ju Han9College of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing 100853, ChinaClinical Hearing Center of Affiliated Hospital of Xuzhou Medical College, Xuzhou, ChinaDepartment of Otorhinolaryngology Head and Neck Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, ChinaCollege of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing 100853, ChinaCollege of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing 100853, ChinaCollege of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing 100853, ChinaDepartment of Communicative Disorders and Sciences, Center for Hearing and Deafness, The State University of New York at Buffalo, Buffalo, New York, USACollege of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing 100853, ChinaCollege of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing 100853, ChinaCollege of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing 100853, ChinaThe objective of this study was to explore the molecular mechanisms of acute noise-induced hearing loss and recovery of steady-state noise-induced hearing loss using miniature pigs. We used miniature pigs exposed to white noise at 120 dB (A) as a model. Auditory brainstem response (ABR) measurements were made before noise exposure, 1 day and 7 days after noise exposure. Proteomic Isobaric Tags for Relative and Absolute Quantification (iTRAQ) was used to observe changes in proteins of the miniature pig inner ear following noise exposure. Western blot and immunofluorescence were performed for further quantitative and qualitative analysis of proteomic changes. The average ABR-click threshold of miniature pigs before noise exposure, 1 day and 7 days after noise exposure, were 39.4 dB SPL, 67.1 dB SPL, and 50.8 dB SPL, respectively. In total, 2,158 proteins were identified using iTRAQ. Both gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) database analyses showed that immune and metabolic pathways were prominently involved during the impairment stage of acute hearing loss. During the recovery stage of acute hearing loss, most differentially expressed proteins were related to cholesterol metabolism. Western blot and immunofluorescence showed accumulation of reactive oxygen species and nuclear translocation of NF-κB (p65) in the hair cells of miniature pig inner ears during the acute hearing loss stage after noise exposure. Nuclear translocation of NF-κB (p65) may be associated with overexpression of downstream inflammatory factors. Apolipoprotein (Apo) A1 and Apo E were significantly upregulated during the recovery stage of hearing loss and may be related to activation of cholesterol metabolic pathways. This is the first study to use proteomics analysis to analyze the molecular mechanisms of acute noise-induced hearing loss and its recovery in a large animal model (miniature pigs). Our results showed that activation of metabolic, inflammatory, and innate immunity pathways may be involved in acute noise-induced hearing loss, while cholesterol metabolic pathways may play an important role in recovery of hearing ability following noise-induced hearing loss.http://dx.doi.org/10.1155/2020/6235948 |
| spellingShingle | Na Sai Xi Shi Yan Zhang Qing-qing Jiang Fei Ji Shuo-long Yuan Wei Sun Wei-Wei Guo Shi-Ming Yang Wei-Ju Han Involvement of Cholesterol Metabolic Pathways in Recovery from Noise-Induced Hearing Loss Neural Plasticity |
| title | Involvement of Cholesterol Metabolic Pathways in Recovery from Noise-Induced Hearing Loss |
| title_full | Involvement of Cholesterol Metabolic Pathways in Recovery from Noise-Induced Hearing Loss |
| title_fullStr | Involvement of Cholesterol Metabolic Pathways in Recovery from Noise-Induced Hearing Loss |
| title_full_unstemmed | Involvement of Cholesterol Metabolic Pathways in Recovery from Noise-Induced Hearing Loss |
| title_short | Involvement of Cholesterol Metabolic Pathways in Recovery from Noise-Induced Hearing Loss |
| title_sort | involvement of cholesterol metabolic pathways in recovery from noise induced hearing loss |
| url | http://dx.doi.org/10.1155/2020/6235948 |
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