Betaine homocysteine S-methyltransferase deficiency causes increased susceptibility to noise-induced hearing loss associated to plasma hyperhomocysteinemia
| Autor: | Murillo-Cuesta, Silvia, Partearroyo, Teresa, Vallecillo, Néstor, Rodriguez-de la Rosa, Lourdes, Celaya, Adelaida M., Mandruzzato, Giacomo, Zeisel, Steven H., Pajares, María A., Varela-Moreiras, Gregorio, Varela-Nieto, Isabel |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España), Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), National Institutes of Health (US) |
| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | Resumen del trabajo presentado al 42st Annual Association for Research in Otolaryngology (ARO) MidWinter Meeting, celebrado en Baltimore, Maryland (USA) del 9 al 13 de febrero de 2019. Nutritional imbalance is an emerging causative factor for deafness and several epidemiological and experimental studies have linked alterations in methionine metabolism caused by folic acid and/or vitamin B12 deficiencies with age-related, noiseinduced or sudden hearing loss. Betaine homocysteine S-methyltransferases (BHMTs) are methionine cycle enzymes that remethylate homocysteine, hence their malfunction leads to hyperhomocysteinemia. Here, we have studied the expression of methionine cycle genes in the mouse cochlea and the impact of knocking out the Bhmt gene in the auditory receptor. We evaluated age-related changes in mouse hearing by recording auditory brainstem responses at different moments from embryonic to adult stages, and following exposure to noise. Also we measured cochlear cytoarchitecture, gene expression by RNA-arrays and RT-qPCR, and metabolite levels in liver and plasma by HPLC. Our results indicate that there is an age-dependent strain-specific expression of methionine cycle genes in the mouse cochlea and a further regulation during the response to noise damage. Loss of Bhmt did not cause an evident impact in the hearing acuity of young mice, but it produced higher threshold shifts and poorer recovery following noise challenge. Hearing loss was associated with increased cochlear injury, altered expression of cochlear methionine cycle genes and hyperhomocysteinemia. Our results suggest that BHMT plays a central role in the homeostasis of cochlear methionine metabolism and that Bhmt2 upregulation could carry out a compensatory role in cochlear protection against noise injury in the absence of BHMT. Work supported by the Spanish MINECO/FEDER SAF2017-86107-R grant to IVN, U.S. National Institutes of Health DK056350 to SZ, and CEU-Banco Santander precompetitive (MUSPB047) and consolidation (MBS18C12) project to TP. |
| Databáze: | OpenAIRE |
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