Nitric oxide protects against cochlear hair cell damage and noise-induced hearing loss through glucose metabolic reprogramming. 2022

Haidi Yang, and Yafeng Zhu, and Yongyi Ye, and Jiao Guan, and Xin Min, and Hao Xiong
Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, Guangzhou, China.

Nitric oxide (NO) is critically involved in the regulation of a wide variety of physiological and pathophysiological processes. However, the role of NO in the pathogenesis of noise-induced hearing loss (NIHL) is complex and remains controversial. Here we reported that treatment of CBA/J mice with l-arginine, a physiological precursor of NO, significantly reduced noise-induced reactive oxygen species accumulation in outer hair cells (OHCs), attenuated noise-induced loss of OHCs and NIHL consequently. Conversely, pharmacological inhibition of endothelial nitric oxide synthase exacerbated noise-induced loss of OHCs and aggravated NIHL. In HEI-OC1 cells, NO also showed substantial protection against H2O2-induced oxidative stress and cytotoxicity. Mechanistically, NO increased S-nitrosylation of pyruvate kinase M2 (PKM2) and inhibited its activity, which thus diverted glucose metabolic flux from glycolysis into the pentose phosphate pathway to increase production of reducing equivalents (NADPH and GSH) and eventually prevented H2O2-induced oxidative damage. These findings open new avenues for protection of cochlear hair cells from oxidative stress and prevention of NIHL through NO modulation of PKM2 and glucose metabolism reprogramming.

UI MeSH Term Description Entries
D008808 Mice, Inbred CBA An inbred strain of mouse that is widely used in BIOMEDICAL RESEARCH. Mice, CBA,Mouse, CBA,Mouse, Inbred CBA,CBA Mice,CBA Mice, Inbred,CBA Mouse,CBA Mouse, Inbred,Inbred CBA Mice,Inbred CBA Mouse
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D003051 Cochlea The part of the inner ear (LABYRINTH) that is concerned with hearing. It forms the anterior part of the labyrinth, as a snail-like structure that is situated almost horizontally anterior to the VESTIBULAR LABYRINTH. Cochleas
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D006317 Hearing Loss, Noise-Induced Hearing loss due to exposure to explosive loud noise or chronic exposure to sound level greater than 85 dB. The hearing loss is often in the frequency range 4000-6000 hertz. Acoustic Trauma,Hearing Loss, Noise Induced,Noise-Induced Hearing Loss
D006861 Hydrogen Peroxide A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. Hydrogen Peroxide (H2O2),Hydroperoxide,Oxydol,Perhydrol,Superoxol,Peroxide, Hydrogen
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018072 Hair Cells, Auditory, Outer Sensory cells of organ of Corti. In mammals, they are usually arranged in three or four rows, and away from the core of spongy bone (the modiolus), lateral to the INNER AUDITORY HAIR CELLS and other supporting structures. Their cell bodies and STEREOCILIA increase in length from the cochlear base toward the apex and laterally across the rows, allowing differential responses to various frequencies of sound. Auditory Hair Cell, Outer,Auditory Hair Cells, Outer,Cochlear Outer Hair Cell,Cochlear Outer Hair Cells,Hair Cell, Auditory, Outer,Hair Cells, Auditory, Outer Inner,Outer Auditory Hair Cell,Outer Auditory Hair Cells,Outer Hair Cells,Hair Cells, Outer

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