Abstract
Oxidative stress is the key determinant in the pathogenesis of noise-induced hearing loss (NIHL). Given that cellular defense against oxidative stress is an energy-consuming process, the aim of the present study was to investigate whether increasing energy availability by glucose supplementation protects cochlear hair cells against oxidative stress and attenuates NIHL. Our results revealed that glucose supplementation reduced the noise-induced formation of reactive oxygen species (ROS) and consequently attenuated noise-induced loss of outer hair cells, inner hair cell synaptic ribbons, and NIHL in CBA/J mice. In cochlear explants, glucose supplementation increased the levels of ATP and NADPH, as well as attenuating H2O2-induced ROS production and cytotoxicity. Moreover, pharmacological inhibition of glucose transporter type 1 activity abolished the protective effects of glucose against oxidative stress in HEI-OC1 cells. These findings suggest that energy availability is crucial for oxidative stress resistance and glucose supplementation offers a simple and effective approach for the protection of cochlear hair cells against oxidative stress and NIHL.
Similar content being viewed by others
References
Cunningham LL, Tucci DL. Restoring synaptic connections in the inner ear after noise damage. N Engl J Med 2015, 372: 181–182.
Henderson D, Bielefeld EC, Harris KC, Hu BH. The role of oxidative stress in noise-induced hearing loss. Ear Hear 2006, 27: 1–19.
Brigande JV, Heller S. Quo vadis, hair cell regeneration? Nat Neurosci 2009, 12: 679–685.
Fetoni AR, De Bartolo P, Eramo SL, Rolesi R, Paciello F, Bergamini C, et al. Noise-induced hearing loss (NIHL) as a target of oxidative stress-mediated damage: cochlear and cortical responses after an increase in antioxidant defense. J Neurosci 2013, 33: 4011–4023.
Sha SH, Schacht J. Emerging therapeutic interventions against noise-induced hearing loss. Expert Opin Investig Drugs 2017, 26: 85–96.
Yuan H, Wang X, Hill K, Chen J, Lemasters J, Yang SM, et al. Autophagy attenuates noise-induced hearing loss by reducing oxidative stress. Antioxid Redox Signal 2015, 22: 1308–1324.
Fetoni AR, Paciello F, Rolesi R, Paludetti G, Troiani D. Targeting dysregulation of redox homeostasis in noise-induced hearing loss: Oxidative stress and ROS signaling. Free Radic Biol Med 2019, 135: 46–59.
Thorne PR, Nuttall AL, Scheibe F, Miller JM. Sound-induced artifact in cochlear blood flow measurements using the laser Doppler flowmeter. Hear Res 1987, 31: 229–234.
Yamane H, Nakai Y, Takayama M, Iguchi H, Nakagawa T, Kojima A. Appearance of free radicals in the guinea pig inner ear after noise-induced acoustic trauma. Eur Arch Otorhinolaryngol 1995, 252: 504–508.
Ohlemiller KK, Wright JS, Dugan LL. Early elevation of cochlear reactive oxygen species following noise exposure. Audiol Neurootol 1999, 4: 229–236.
Zhang G, Zheng H, Pyykko I, Zou J. The TLR-4/NF-kappaB signaling pathway activation in cochlear inflammation of rats with noise-induced hearing loss. Hear Res 2019, 379: 59–68.
Xiong H, Ou Y, Xu Y, Huang Q, Pang J, Lai L, et al. Resveratrol promotes recovery of hearing following intense noise exposure by enhancing cochlear SIRT1 activity. Audiol Neurootol 2017, 22: 303–310.
Martindale JL, Holbrook NJ. Cellular response to oxidative stress: signaling for suicide and survival. J Cell Physiol 2002, 192: 1–15.
Yu XJ, Zhao YN, Hou YK, Li HB, Xia WJ, Gao HL, et al. Chronic intracerebroventricular infusion of metformin inhibits salt-sensitive hypertension via attenuation of oxidative stress and neurohormonal excitation in rat paraventricular nucleus. Neurosci Bull 2019, 35: 57–66.
Liu AH, Chu M, Wang YP. Up-regulation of Trem2 inhibits hippocampal neuronal apoptosis and alleviates oxidative stress in epilepsy via the PI3K/Akt pathway in mice. Neurosci Bull 2019, 35: 471–485.
Mergenthaler P, Lindauer U, Dienel GA, Meisel A. Sugar for the brain: the role of glucose in physiological and pathological brain function. Trends Neurosci 2013, 36: 587–597.
Chen FQ, Zheng HW, Hill K, Sha SH. Traumatic noise activates Rho-family GTPases through transient cellular energy depletion. J Neurosci 2012, 32: 12421–12430.
Munoz DJ, Kendrick IS, Rassam M, Thorne PR. Vesicular storage of adenosine triphosphate in the guinea-pig cochlear lateral wall and concentrations of ATP in the endolymph during sound exposure and hypoxia. Acta Otolaryngol 2001, 121: 10–15.
Vlajkovic SM, Housley GD, Munoz DJ, Robson SC, Sevigny J, Wang CJ, et al. Noise exposure induces up-regulation of ecto-nucleoside triphosphate diphosphohydrolases 1 and 2 in rat cochlea. Neuroscience 2004, 126: 763–773.
Riahi H, Brekelmans C, Foriel S, Merkling SH, Lyons TA, Itskov PM, et al. The histone methyltransferase G9a regulates tolerance to oxidative stress-induced energy consumption. PLoS Biol 2019, 17: e2006146.
Xiong H, Pang J, Yang H, Dai M, Liu Y, Ou Y, et al. Activation of miR-34a/SIRT1/p53 signaling contributes to cochlear hair cell apoptosis: implications for age-related hearing loss. Neurobiol Aging 2015, 36: 1692–1701.
Xiong H, Long H, Pan S, Lai R, Wang X, Zhu Y, et al. Inhibition of histone methyltransferase G9a attenuates noise-induced cochlear synaptopathy and hearing loss. J Assoc Res Otolaryngol 2019, 20: 217–232.
Xiong H, Chen S, Lai L, Yang H, Xu Y, Pang J, et al. Modulation of miR-34a/SIRT1 signaling protects cochlear hair cells against oxidative stress and delays age-related hearing loss through coordinated regulation of mitophagy and mitochondrial biogenesis. Neurobiol Aging 2019, 79: 30–42.
Benkafadar N, Francois F, Affortit C, Casas F, Ceccato JC, Menardo J, et al. ROS-induced activation of DNA damage responses drives senescence-like state in postmitotic cochlear cells: implication for hearing preservation. Mol Neurobiol 2019, 56: 5950–5969.
Wu F, Xiong H, Sha S. Noise-induced loss of sensory hair cells is mediated by ROS/AMPKalpha pathway. Redox Biol 2020, 29: 101406.
Sha SH, Zajic G, Epstein CJ, Schacht J. Overexpression of copper/zinc-superoxide dismutase protects from kanamycin-induced hearing loss. Audiol Neurootol 2001, 6: 117–123.
Keithley EM, Canto C, Zheng QY, Wang X, Fischel-Ghodsian N, Johnson KR. Cu/Zn superoxide dismutase and age-related hearing loss. Hear Res 2005, 209: 76–85.
Ohlemiller KK, McFadden SL, Ding DL, Flood DG, Reaume AG, Hoffman EK, et al. Targeted deletion of the cytosolic Cu/Zn-superoxide dismutase gene (Sod1) increases susceptibility to noise-induced hearing loss. Audiol Neurootol 1999, 4: 237–246.
Ren Y, Li Y, Yan J, Ma M, Zhou D, Xue Z, et al. Adiponectin modulates oxidative stress-induced mitophagy and protects C2C12 myoblasts against apoptosis. Sci Rep 2017, 7: 3209.
Choi HI, Kim HJ, Park JS, Kim IJ, Bae EH, Ma SK, et al. PGC-1alpha attenuates hydrogen peroxide-induced apoptotic cell death by upregulating Nrf-2 via GSK3beta inactivation mediated by activated p38 in HK-2 Cells. Sci Rep 2017, 7: 4319.
Fan J, Ye J, Kamphorst JJ, Shlomi T, Thompson CB, Rabinowitz JD. Quantitative flux analysis reveals folate-dependent NADPH production. Nature 2014, 510: 298–302.
Macintyre AN, Gerriets VA, Nichols AG, Michalek RD, Rudolph MC, Deoliveira D, et al. The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function. Cell Metab 2014, 20: 61–72.
Howarth C, Gleeson P, Attwell D. Updated energy budgets for neural computation in the neocortex and cerebellum. J Cereb Blood Flow Metab 2012, 32: 1222–1232.
Pascual JM, Wang D, Hinton V, Engelstad K, Saxena CM, Van Heertum RL, et al. Brain glucose supply and the syndrome of infantile neuroglycopenia. Arch Neurol 2007, 64: 507–513.
Garriga-Canut M, Schoenike B, Qazi R, Bergendahl K, Daley TJ, Pfender RM, et al. 2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure. Nat Neurosci 2006, 9: 1382–1387.
Kapogiannis D, Mattson MP. Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer’s disease. Lancet Neurol 2011, 10: 187–198.
Borghammer P, Hansen SB, Eggers C, Chakravarty M, Vang K, Aanerud J, et al. Glucose metabolism in small subcortical structures in Parkinson’s disease. Acta Neurol Scand 2012, 125: 303–310.
Frisina ST, Mapes F, Kim S, Frisina DR, Frisina RD. Characterization of hearing loss in aged type II diabetics. Hear Res 2006, 211: 103–113.
Gupta S, Eavey RD, Wang M, Curhan SG, Curhan GC. Type 2 diabetes and the risk of incident hearing loss. Diabetologia 2019, 62: 281–285.
Manzo E, Lorenzini I, Barrameda D, O’Conner AG, Barrows JM, Starr A, et al. Glycolysis upregulation is neuroprotective as a compensatory mechanism in ALS. Elife 2019, 8. https://doi.org/10.7554/elife.45114.
Fettiplace R, Hackney CM. The sensory and motor roles of auditory hair cells. Nat Rev Neurosci 2006, 7: 19–29.
LeMasurier M, Gillespie PG. Hair-cell mechanotransduction and cochlear amplification. Neuron 2005, 48: 403–415.
Butterfield DA, Halliwell B. Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease. Nat Rev Neurosci 2019, 20: 148–160.
Kim YR, Baek JI, Kim SH, Kim MA, Lee B, Ryu N, et al. Therapeutic potential of the mitochondria-targeted antioxidant MitoQ in mitochondrial-ROS induced sensorineural hearing loss caused by Idh2 deficiency. Redox Biol 2019, 20: 544–555.
Ji L, Lee HJ, Wan G, Wang GP, Zhang L, Sajjakulnukit P, et al. Auditory metabolomics, an approach to identify acute molecular effects of noise trauma. Sci Rep 2019, 9: 9273.
Acknowledgements
This work was supported by the National Natural Science Foundation of China (81570916, 81771018, and 81873699).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors claim that there are no conflicts of interest.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Xiong, H., Lai, L., Ye, Y. et al. Glucose Protects Cochlear Hair Cells Against Oxidative Stress and Attenuates Noise-Induced Hearing Loss in Mice. Neurosci. Bull. 37, 657–668 (2021). https://doi.org/10.1007/s12264-020-00624-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12264-020-00624-1