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Premature hearing loss concurs with alterations in proteins of homocysteine metabolism

AutorGarrido, Francisco ; Martínez-Vega, Raquel ; Varela-Moreiras, Gregorio; Partearroyo, Teresa; Martínez-Álvarez, Concepción; Varela-Nieto, Isabel ; Pajares, María A.
Fecha de publicación2013
Citación27th Annual Symposium of the Protein Society: (2013)
ResumenS-adenosylhomocysteine hydrolase (SAHH), betaine homocysteine methyltransferase (BHMT), methionine synthase (MS) and cystathionine ß-synthase (CBS) are the enzymes responsible for homocysteine (Hcy) metabolism. SAHH generates Hcy by hydrolisis of SAH, a product of transmethylation reactions, whereas BHMT and MS remethylate Hcy to recover methionine using betaine and methyltetrahydrofolate, respectively1. Additionally, Hcy can be eliminated by CBS in the first reaction of the trans-sulfuration pathway or secreted into the plasma leading to hyperhomocysteinemia (HHcy). Hcy metabolism is regulated by nutritional factors, including vitamins that are cofactors of several steps. Alterations in plasma Hcy (pHcy) levels were detected in a variety of diseases, including deafness. Association between HHcy and hearing loss was further suggested in several animal models2 and in human nutritional studies. In this work we have studied the impact of a dietary-induced folic acid deficiency (FAD) on the cochlear Hcy metabolism and in hearing. Our results showed that FAD induces premature hearing loss in the C57BL/6J mouse model, as assessed by ABR threshold. Expression changes in several cochlear enzymes of Hcy metabolism by real-time PCR and western blot were detected. Plasma metabolite levels were measured by HPLC, showing the expected folic acid reductions together with elevated pHcy levels. Several proteins of Hcy metabolism showed altered mobility in western blot as compared to liver patterns, suggesting post-translational modifications in this organ that are being analyzed by mass spectrometry. In conclusion, our data indicate that all the enzymes of Hcy metabolism are expressed in the cochlea, alterations in mRNA and protein levels correlating with hearing loss and elevations of pHcy.
DescripciónPóster presentado al 27th Annual Symposium of the Protein Society, celebrado en Boston (US) del 20 al 23 de julio de 2013.
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