Reduced Phosphorylation of Histone Variant H2Ax in the Organ of Corti is Associated with Otoprotection from Noise Injury

Abstract

Research on the molecular bases of noise induced hearing loss has revealed that noise exposure produces multiple independent and complementary biochemical cascades that could damage DNA. The phosphorylation of Ser139 of histone variant H2Ax (γ-H2Ax) occurs within one minute following DNA damage and spans two million DNA bases on either side of the damage. In the current study we investigated whether noise exposure could induce γ-H2Ax within the organ of Corti. Cumulative signal strength was employed to quantify the absolute level of γ-H2Ax in mathematical energy units. The results indicated that noise exposure could increase the level of γ-H2Ax in the organ of Corti. Furthermore, treatment with a DNA repair enhancing chemotype (carboxy alkyl ester) reduced the noise induced increase of γ-H2Ax which was associated with an accelerated rate of functional recovery from the noise exposure. The combined results implicate molecular mechanisms of DNA damage and repair in the pathophysiology of noise induced hearing loss.