Abnormal Cholesterol Metabolism and Lysosomal Dysfunction Induce Age-Related Hearing Loss by Inhibiting mTORC1-TFEB-Dependent Autophagy
Abstract
:1. Introduction
2. Results
2.1. Metabolic Disease-Related Gene Expression in Cochlear Tissues
2.2. mTORC1 Activity, TFEB Expression, Lysosomal Damage, and Autophagic Flux Inhibition in Cochlear Tissues
2.3. In Vivo Phenotype and Stress-Induced Premature Senescence Models of HEI-OC1 Cells
2.4. Regulation of Lysosomal Biosynthesis and Autophagic Turnover by the mTORC1-TFEB Pathway during SIPS
2.5. Atorvastatin Regulates Lysosomal Biosynthesis and Autophagic Activity by Decreasing mTORC1 Activity and Increasing TFEB Expression
2.6. AS Maintains TFEB-Mediated Lysosomal Biogenesis and Autophagic Turnover in Cochlear Tissues with ARHL
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. Auditory Brainstem Response Analysis
4.3. Cell Culture and Doxorubicin Treatment
4.4. Immunoblotting
4.5. Hematoxylin and Eosin and Immunohistochemical Staining
4.6. Cholesterol Content
4.7. Filipin Staining
4.8. Electron Microscopy
4.9. Real-Time PCR
4.10. siRNA Transfection
4.11. Plasmid Transfection
4.12. RNA Sequencing
4.13. Gene Enrichment and Functional Annotation Analyses
4.14. Gene Set Enrichment Analysis
4.15. Ingenuity Pathway Analysis
4.16. Antibodies and Reagents
4.17. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Lee, Y.Y.; Ha, J.; Kim, Y.S.; Ramani, S.; Sung, S.; Gil, E.S.; Choo, O.-S.; Jang, J.H.; Choung, Y.-H. Abnormal Cholesterol Metabolism and Lysosomal Dysfunction Induce Age-Related Hearing Loss by Inhibiting mTORC1-TFEB-Dependent Autophagy. Int. J. Mol. Sci. 2023, 24, 17513. https://doi.org/10.3390/ijms242417513
Lee YY, Ha J, Kim YS, Ramani S, Sung S, Gil ES, Choo O-S, Jang JH, Choung Y-H. Abnormal Cholesterol Metabolism and Lysosomal Dysfunction Induce Age-Related Hearing Loss by Inhibiting mTORC1-TFEB-Dependent Autophagy. International Journal of Molecular Sciences. 2023; 24(24):17513. https://doi.org/10.3390/ijms242417513
Chicago/Turabian StyleLee, Yun Yeong, Jungho Ha, Young Sun Kim, Sivasubramanian Ramani, Siung Sung, Eun Sol Gil, Oak-Sung Choo, Jeong Hun Jang, and Yun-Hoon Choung. 2023. "Abnormal Cholesterol Metabolism and Lysosomal Dysfunction Induce Age-Related Hearing Loss by Inhibiting mTORC1-TFEB-Dependent Autophagy" International Journal of Molecular Sciences 24, no. 24: 17513. https://doi.org/10.3390/ijms242417513