Suppressed expression of LDHB promotes age-related hearing loss via aerobic glycolysis.

Chunjie Tian, Yeon Ju Kim, Sai Hali, Oak-Sung Choo, Jin-Sol Lee, Seo-Kyung Jung, Youn-Uk Choi, Chan Bae Park, Yun-Hoon Choung

Cell death & disease 2020 May 15

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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.

Citation

Chunjie Tian, Yeon Ju Kim, Sai Hali, Oak-Sung Choo, Jin-Sol Lee, Seo-Kyung Jung, Youn-Uk Choi, Chan Bae Park, Yun-Hoon Choung. Suppressed expression of LDHB promotes age-related hearing loss via aerobic glycolysis. Cell death & disease. 2020 May 15;11(5):375