Suppressed expression of LDHB promotes age-related hearing loss via aerobic glycolysis
| Autor: | Yun-Hoon Choung, Seo-Kyung Jung, Yeonju Kim, Chan Bae Park, Oak-Sung Choo, Jin-Sol Lee, Chunjie Tian, Sai Hali, Youn-Uk Choi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Translation Cancer Research Immunology Article Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Downregulation and upregulation Cell Line Tumor Pyruvic Acid medicine Animals Glycolysis Lactic Acid lcsh:QH573-671 Hearing Loss Inner mitochondrial membrane Gene knockdown L-Lactate Dehydrogenase Chemistry lcsh:Cytology Age Factors Cell Biology Mitochondria Cell biology Isoenzymes 030104 developmental biology medicine.anatomical_structure Organ of Corti Anaerobic glycolysis Knockout mouse NAD+ kinase Neurological disorders 030217 neurology & neurosurgery |
| Zdroj: | Cell Death and Disease, Vol 11, Iss 5, Pp 1-13 (2020) Cell Death & Disease |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-020-2577-y |
| Popis: | Age-dependent decrease of mitochondrial energy production and cellular redox imbalance play significant roles in age-related hearing loss (ARHL). Lactate dehydrogenase B (LDHB) is a key glycolytic enzyme that catalyzes the interconversion of pyruvate and lactate. LDH activity and isoenzyme patterns are known to be changed with aging, but the role of LDHB in ARHL has not been studied yet. Here, we found that LDHB knockout mice showed hearing loss at high frequencies, which is the typical feature of ARHL. LDHB knockdown caused downregulation of mitochondrial functions in auditory cell line, University of Bristol/organ of Corti 1 (UB/OC1) with decreased NAD+ and increased hypoxia inducing factor-1α. LDHB knockdown also enhanced the death of UB/OC1 cells with ototoxic gentamicin treatment. On the contrary, the induction of LDHB expression caused enhanced mitochondrial functions, including changes in mitochondrial respiratory subunits, mitochondrial membrane potentials, ATP, and the NAD+/NADH ratio. Thus, we concluded that suppression of LDHB activity may be closely related with the early onset or progression of ARHL. |
| Databáze: | OpenAIRE |
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