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Publication : The SIRT2 inhibitor AK-7 decreases cochlear cell apoptosis and attenuates noise-induced hearing loss.

First Author  Liu Y Year  2019
Journal  Biochem Biophys Res Commun Volume  509
Issue  3 Pages  641-646
PubMed ID  30616888 Mgi Jnum  J:300646
Mgi Id  MGI:6442216 Doi  10.1016/j.bbrc.2018.12.084
Citation  Liu Y, et al. (2019) The SIRT2 inhibitor AK-7 decreases cochlear cell apoptosis and attenuates noise-induced hearing loss. Biochem Biophys Res Commun 509(3):641-646
abstractText  Oxidative damage plays a critical role in cochlear cell apoptosis, which is central to the physiopathology of noise-induced hearing loss (NIHL). Sirtuin 2 (SIRT2) is an NAD-dependent deacetylase that regulates cellular response to oxidative stress, however, its role in NIHL remains poorly understood. Here, we report that SIRT2 is upregulated in the cochlea after noise exposure. Functionally, the treatment of AK-7, one specific SIRT2 inhibitor, attenuates the progression of NIHL. In addition, AK-7 treatment reduces oxidative nuclear DNA damage and apoptosis in the cochlea after noise exposure. Moreover, AK-7 treatment reduces apoptosis of mouse inner ear HEI-OC1 cells exposed to oxidative stress in vitro. Taken together, these results suggest that SIRT2 inhibition with AK-7 reduces cochlear cell apoptosis through attenuating oxidative stress-induced damage, which may underlie its protective role against NIHL. This study also implies that AK-7 may have potential therapeutic significance in the intervention of NIHL.
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