ArticleFrontiers in cellular neuroscience2023
Prevention of noise-induced hearing loss by calpain inhibitor MDL-28170 is associated with upregulation of PI3K/Akt survival signaling pathway.
Article in Frontiers in cellular neuroscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 16 citations in OpenAlex.
- MLL1 downregulation drives hair cell ferroptosis via mitochondrial and endoplasmic reticulum stress mechanisms through PERK-eIF2α-ATF4-Chop and PI3K/Akt-Lrp1 signaling pathway.Chinese medical journal · 2026Article
- The Piezo1-Ca2+-PI3k/Akt signaling axis as a context-dependent mechanotransduction node during skin wound healing.iScience · 2026Review
- Furosemide prevents noise-induced hearing loss and enhances the preventive effect of N-acetylcysteine.Hearing research · 2026Article
- A Regulator SNP Affecting the Transcription FactorHuman mutation · 2026Article
- Serum CAPN1 and CLEC2 as Biomarkers for Hearing Loss Severity and Internal Auditory Artery Narrowing in Sudden Sensorineural Hearing Loss.International journal of general medicine · 2026Article
- Review
- Comparative Cochlear Transcriptomics in Echolocating Bats and Mouse Reveals Hras as Protector Against Noise-Induced Hearing Loss.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Alterations of Photoreceptor Synaptic Ribbons in the Retina of a Human Patient With Oculocutaneous Albinism Type 1 (OCA1).Investigative ophthalmology & visual science · 2025Article
- 5xFAD mutations induce hearing impairment in the Ahl-corrected 5xFAD mice.Experimental neurology · 2025Article
- Exploring AAV-Mediated Gene Therapy for Inner Ear Diseases: from Preclinical Success to Clinical Potential.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Noise-Induced Hearing Loss: Overview and Future Prospects for Research on Oxidative Stress.International journal of molecular sciences · 2025Review
- Hesperidin activates Nrf2 to protect cochlear hair cells from cisplatin-induced damage.Redox report : communications in free radical research · 2024Article
- Effects of Astragaloside IV on Hearing, Inflammatory Factors, and Intestinal Flora in Mice Exposed to Noise.Metabolites · 2024Article
- Modeling of auditory neuropathy spectrum disorders associated with theFrontiers in molecular neuroscience · 2024Article
- Study on Screening Core Biomarkers of Noise and Drug-Induced Hearing Loss Based on Transcriptomics.Global medical genetics · 2023Article
- Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Introduction: Noise-induced calcium overload in sensory hair cells has been well documented as an early step in the pathogenesis of noise-induced hearing loss (NIHL). Alterations in cellular calcium homeostasis mediate a series of cellular events, including activation of calcium-dependent protein kinases and phosphatases. Using cell-membrane- and blood-brain-barrier-permeable calpain-1 (μ-calpain) and calpain-2 (m-calpain) inhibitor MDL-28170, we tested the involvement of calpains, a family of calcium-dependent cysteine proteases, and the potential of MDL-28170 in preventing NIHL. Methods: CBA/J mice at the age of 12 weeks were exposed to broadband noise with a frequency spectrum from 2-20 kHz for 2 h at 101 dB sound pressure level to induce permanent hearing loss as measured by auditory brainstem response and distortion product otoacoustic emissions. Morphological damage was assessed by quantification of remaining sensory hair cells and inner hair cell synapses 2 weeks after the exposure. Results: MDL-28170 treatment by intraperitoneal injection significantly attenuated noise-induced functional deficits and cochlear pathologies. MDL-28170 treatment also prevented noise-induced cleavage of alpha-fodrin, a substrate for calpain-1. Furthermore, MDL-28170 treatment prevented reduction of PI3K/Akt signaling after exposure to noise and upregulated p85α and p-Akt (S473) in outer hair cells. Discussion: These results indicate that noise-induced calpain activation negatively regulates PI3K/Akt downstream signaling, and that prevention of NIHL by treatment with MDL-28170 is associated with upregulation of PI3K/Akt survival signaling pathways.
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Registered trials
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