Methylation of GLUT5 and Electromotile Responses During Chronic and Acute Sodium Salicylate Administration in the Cochlear Outer Hair Cells

Year 2024, Volume: 14 Issue: 1, 72 - 79, 30.04.2024

Mustafa Yıldız , Metin Budak Züleyha Dilek Gülmez Erdoğan Bulut

Abstract

Aim: Prestin molecule and transporter fructose GLUT5 in the lateral walls of outer hair cells are essential. This study aimed to investigate epigenetic alterations in the GLUT5 gene.
Materials and methods: The animals were divided into three groups randomly. No injection was received in the first group (n=3). Groups 2(n=3) and 3(n=6) were injected with intramuscular saline and sodium salicylate, respectively. Electrophysiological measurements were performed at 1st, 2nd, and 8th hours to evaluate the acute effect and in 2 weeks to evaluate the chronic effect. Methylation of CpG dinucleotides in the promoter can lead to dysregulated and repressed gene expression. Genomic DNA was isolated from bone tissues, treated with bisulfite, and analyzed using methylation specific PCR (polymerase chain reaction) (MSP). Epigenetic alterations in the GLUT5 gene were investigated by using the MSP method.
Results: There was a significant decrease in electrophysiological measurements at all frequencies in the acute effect (p<0.01), whereas there was no significant difference in the chronic effect for Group 3 (p>0.05). However, methylation of GLUT5 was observed to be increased during acute administration, followed by a decreasing trend to normal during the chronic period.
Conclusion: Our findings show that methylation of GLUT5 may decrease GLUT5 expression in lateral walls of outer hair cells, thereby changing prestin-bound fructose transport in cell membranes due to reduced GLUT5 expression.

Keywords

GLUT5, outer hair cells, cochlea, distortion product otoacoustic emissions; sodium salicylate

References

• 1. Ashmore J. Cochlear outer hair cell motility. Physiol Rev. 2008;88(1):173–210.
• 2. Fettiplace R. Hair cell transduction, tuning, and synaptic transmission in the mammalian cochlea. Comprehensive Physiology. 2011;7(4):1197–227.
• 3. Kachar B, Brownell WE, Altschuler R, Fex J. Electrokinetic shape changes of cochlear outer hair cells. Nature. 1986;322(6077):365–8.
• 4. Zheng J, Shen W, He DZ, Long KB, Madison LD, Dallos P. Prestin is the motor protein of cochlear outer hair cells. Nature. 2000;405(6783):149–55.
• 5. Dallos P, Wu X, Cheatham MA, Gao J, Zheng J, Anderson CT, et al. Prestin-based outer hair cell motility is necessary for mammalian cochlear amplification. Neuron. 2008;58(3):3339.
• 6. Bai JP, Navaratnam D, Santos-Sacchi J. Prestin kinetics and corresponding frequency dependence augment during early development of the outer hair cell within the mouse organ of Corti. Sci Rep. 2019;9(1):16460.
• 7. Nakazawa K, Spicer SS, Schulte BA. Postnatal expression of the facilitated glucose transporter, GLUT 5, in gerbil outer hair cells. Hear Res. 1995;82(1):93–9.
• 8. Wu X, Wang X, Gao J, Yu Y, Jia S, Zheng J, et al. Glucose transporter 5 is undetectable in outer hair cells and does not contribute to cochlear amplification. Brain Res. 2008;1210:208.
• 9. Parham K, Sohal M, Petremann M, Romanet C, Broussy A, Tran Van Ba C, et al. Noise-induced trauma produces a temporal pattern of change in blood levels of the outer hair cell biomarker prestin. Hear Res. 2019;371:98–104.
• 10. Wu X, Currall B, Yamashita T, Parker LL, Hallworth R, Zuo J. Prestin-prestin and prestin-GLUT5 interactions in HEK293T cells. Dev Neurobiol. 2007;67(4):483–97.
• 11. Matsuoka K, Wada K, Miyasaka Y, Yasuda SP, Seki Y, Nishito Y, et al. OHC-TRECK. A Novel System Using a Mouse Model for Investigation of the Molecular Mechanisms Associated with Outer Hair Cell Death in the Inner Ear. Sci Rep. 2019;9(1):5285.
• 12. Yang K, Huang ZW, Liu ZQ, Xiao BK, Peng JH. Long-term administration of salicylate enhances prestin expression in rat cochlea. Int J Audiol. 2009;48(1):18–23.
• 13. Oliver D, He DZ, Klocker N, Ludwig J, Schulte U, Waldegger S, et al. Intracellular anions as the voltage sensor of prestin, the outer hair cell motor protein. Science. 2001;292(5525):23403.
• 14. Hakizimana P, Fridberger A. Effects of salicylate on soundevoked outer hair cell stereocilia deflections. Pflugers Arch. 2015;467(9):2021–9.
• 15. Tunstall MJ, Gale JE, Ashmore JF. Action of salicylate on membrane capacitance of outer hair cells from the guinea-pig cochlea. J Physiol. 1995;485(Pt 3)(3):739–52.
• 16. Chen B, Wang Y, Geng M, Lin X, Tang W. Localization of Glucose Transporter 10 to Hair Cells’ Cuticular Plate in the Mouse Inner Ear. Biomed Res Int. 2018;2018:7817453.
• 17. Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet. 2003;33 Suppl (3):245–54.
• 18. Brenet F, Moh M, Funk P, Feierstein E, Viale AJ, Socci ND, et al. DNA methylation of the first exon is tightly linked to transcriptional silencing. PLoS One. 2011;6(1):e14524.
• 19. Geleoc GS, Casalotti SO, Forge A, Ashmore JF. A sugar transporter as a candidate for the outer hair cell motor. Nat Neurosci. 1999;2(8):713–9.
• 20. Chang A, Chen P, Guo S, Xu N, Pan W, Zhang H, et al. Specific Influences of Early Acoustic Environments on Cochlear Hair Cells in Postnatal Mice. Neural Plast. 2018;2018:5616930.
• 21. Jiang M, Karasawa T, Steyger PS. Aminoglycoside-Induced Cochleotoxicity: A Review. Front Cell Neurosci. 2017;11:308.
• 22. Chen GD, Kermany MH, D’Elia A, Ralli M, Tanaka C, Bielefeld EC, et al. Too much of a good thing: long-term treatment with salicylate strengthens outer hair cell function but impairs auditory neural activity. Hear Res. 2010;265(1–2):63–9.
• 23. Radziwon KE, Stolzberg DJ, Urban ME, Bowler RA, Salvi RJ. Salicylate-induced hearing loss and gap detection deficits in rats. Front Neurol. 2015;6:31.
• 24. Bulut E, Budak M, Ozturk L, Turkmen MT, Uzun C, Sipahi T. DNA methylation of the prestin gene and outer hair cell electromotileresponse of the cochlea in salicylate administration. Turk J Med Sci. 2017;47(5):1626–33.
• 25. Huang ZW, Luo Y, Wu Z, Tao Z, Jones RO, Zhao HB. Paradoxical enhancement of active cochlear mechanics in long-term administration of salicylate. J Neurophysiol. 2005;93(4):2053–61.
• 26. Yu N, Zhu ML, Johnson B, Liu YP, Jones RO, Zhao HB. Prestin up-regulation in chronic salicylate (aspirin) administration: an implication of functional dependence of prestin expression. Cell Mol Life Sci. 2008;65(15):2407–18.
• 27. Li LC, Dahiya R. MethPrimer: designing primers for methylation PCRs. Bioinformatics. 2002;18(11):1427–31.
• 28. Bharati J, Dangi SS, Mishra SR, Chouhan VS, Verma V, Shankar O, et al. Expression analysis of Toll like receptors and interleukins in Tharparkar cattle during acclimation to heat stress exposure. J Therm Biol. 2017;65:48–56.
• 29. Godfrey KM, Lillycrop KA, Burdge GC, Gluckman PD, Hanson MA. Epigenetic mechanisms and the mismatch concept of the developmental origins of health and disease. Pediatric research. 2007;61(7):5–10.
• 30. Ralli M, Troiani D, Podda MV, Paciello F, Eramo S, De Corso E, et al. The effect of the NMDA channel blocker memantine on salicylate-induced tinnitus in rats. Acta Otorhinolaryngologica Italica. 2014;34(3):198