ArticleMolecular medicine (Cambridge, Mass.)2022
AAV-ie-mediated UCP2 overexpression accelerates inner hair cell loss during aging in vivo.
Article in Molecular medicine (Cambridge, Mass.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 11 citations in OpenAlex.
- Therapeutic Timing at Mitochondrial Redox-Autophagy-Mitophagy Checkpoints in Age-Related Hearing Loss.Molecular neurobiology · 2026Review
- Deciphering Uncoupling Proteins in Cellular Homeostasis and Metabolic Health.International journal of biological sciences · 2026Review
- Neural stem cell-loaded biohybrid hydrogel improves cochlear implants by electrode-neural coupling and neural regeneration.Theranostics · 2026Article
- Precision Diagnostics in Age-Related Hearing Loss: Emerging Molecular Biomarkers for Early Detection and Targeted Prevention.International journal of general medicine · 2026Review
- Presbycusis: Pathology, Signal Pathways, and Therapeutic Strategy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Inhibition of TLR4 mitigates sensorineural hearing loss resulting from cochlear inflammation.Molecular medicine (Cambridge, Mass.) · 2025Article
- mRNA metabolism regulator human antigen R (HuR) regulates age-related hearing loss in aged mice.Nature aging · 2025Article
- Review
- Genipin attenuates oxidative damage in periodontal tissues by alleviating mitochondrial dysfunction and abnormal glucose uptake through inhibition of UCP2.Frontiers in pharmacology · 2025Article
- Emerging role and the signaling pathways of uncoupling protein 2 in kidney diseases.Renal failure · 2024Review
- D-Galactose and Hypoxia Induce the Early Onset of Age-Related Hearing Loss Deterioration in a Mouse Model.Tissue engineering and regenerative medicine · 2023Article
- Peroxisome Deficiency in Cochlear Hair Cells Causes Hearing Loss by Deregulating BK Channels.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
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Authors and funding
6 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundUncoupling protein 2 (UCP2), activated by excessive reactive oxygen species (ROS) in vivo, has the dual effect of reducing ROS to protect against oxidative stress and reducing ATP production to regulate cellular metabolism. Both the UCP2 and ROS are increased in cochleae in age-related hearing loss (ARHL). However, the role of UCP2 in sensory hair cells in ARHL remains unclear.
methodsMale C57BL/6 J mice were randomly assigned to an 8-week-old group (Group 1), a 16-week-old group (Group 2), a 16-week-old + adeno-associated virus-inner ear (AAV-ie) group (Group 3), and a 16-week-old + AAV-ie-UCP2 group (Group 4). Mice aged 8 weeks were administrated with AAV-ie-GFP or AAV-ie-UCP2 via posterior semicircular canal injection. Eight weeks after this viral intervention, hearing thresholds and wave-I amplitudes were tested by auditory brainstem response (ABR). Subsequently, the cochlear basilar membrane was dissected for investigation. The number of hair cells and inner hair cell (IHC) synapses, the level of ROS, and the expression of AMP-activated protein kinase α (AMPKα), were assessed by immunofluorescence staining. In addition, mitochondrial function was determined, and the expression of AMPKα and UCP2 proteins was further evaluated using western blotting.
resultsMice with early-onset ARHL exhibited enhanced oxidative stress and loss of outer hair cells and IHC synapses, while UCP2 overexpression aggravated hearing loss and cochlear pathophysiological changes in mice. UCP2 overexpression resulted in a notable decrease in the number of IHCs and IHC synapses, caused ATP depletion and excessive ROS generation, increased AMPKα protein levels, and promoted IHC apoptosis, especially in the apical and middle turns of the cochlea.
conclusionCollectively, our data suggest that UCP2 overexpression may cause mitochondrial dysfunction via energy metabolism, which activates mitochondrion-dependent cellular apoptosis and leads to IHC loss, ultimately exacerbating ARHL.
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