2024-03-28T21:42:05Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1243432021-12-27T16:12:14Zcom_10261_22com_10261_1col_10261_275
2015-11-03T10:51:08Z
urn:hdl:10261/124343
Folic acid deficiency induces premature hearing loss through mechanisms involving cochlear oxidative stress and impairment of homocysteine metabolism
Martínez-Vega, Raquel
Garrido, Francisco
Partearroyo, Teresa
Cediel, Rafael
Zeisel, Steven H.
Martínez-Álvarez, Concepción
Varela-Moreiras, Gregorio
Varela-Nieto, Isabel
Pajares, María A.
Consejo Superior de Investigaciones Científicas (España)
Ministerio de Ciencia e Innovación (España)
European Commission
National Institutes of Health (US)
Puleva
Methionine cycle
Hair cell loss
Apoptosis
Dietary restriction
Hyperhomocysteinemia
Nutritional imbalance is emerging as a causative factor of hearing loss. Epidemiologic studies have linked hearing loss to elevated plasma total homocysteine (tHcy) and folate deficiency, and have shown that folate supplementation lowers tHcy levels potentially ameliorating age-related hearing loss. The purpose of this study was to address the impact of folate deficiency on hearing loss and to examine the underlying mechanisms. For this purpose, 2-mo-old C57BL/6J mice (Animalia Chordata Mus musculus) were randomly divided into 2 groups (n = 65 each) that were fed folate-deficient (FD) or standard diets for 8 wk. HPLC analysis demonstrated a 7-fold decline in serum folate and a 3-fold increase in tHcy levels. FD mice exhibited severe hearing loss measured by auditory brainstem recordings and TUNEL-positive-apoptotic cochlear cells. RT-quantitative PCR and Western blotting showed reduced levels of enzymes catalyzing homocysteine (Hcy) production and recycling, together with a 30% increase in protein homocysteinylation. Redox stress was demonstrated by decreased expression of catalase, glutathione peroxidase 4, and glutathione synthetase genes, increased levels of manganese superoxide dismutase, and NADPH oxidase-complex adaptor cytochrome b-245, α-polypeptide (p22phox) proteins, and elevated concentrations of glutathione species. Altogether, our findings demonstrate, for the first time, that the relationship between hyperhomocysteinemia induced by folate deficiency and premature hearing loss involves impairment of cochlear Hcy metabolism and associated oxidative stress.
2015-11-03T10:51:08Z
2015-11-03T10:51:08Z
2015
2015-11-03T10:51:09Z
artículo
FASEB Journal 29(2): 418-432 (2015)
http://hdl.handle.net/10261/124343
10.1096/fj.14-259283
http://dx.doi.org/10.13039/501100003339
http://dx.doi.org/10.13039/501100004837
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/100000002
25384423
eng
Preprint
https://doi.org/10.1096/fj.14-259283
Sí
info:eu-repo/grantAgreement/EC/FP7/304900
info:eu-repo/grantAgreement/EC/FP7/612261
openAccess
Federation of American Societies for Experimental Biology