Nitric oxide protects against cochlear hair cell damage and noise-induced hearing loss through glucose metabolic reprogramming.
Nitric oxide protects against cochlear hair cell damage and noise-induced hearing loss through glucose metabolic reprogramming.
复制标题
DOI：
10.1016/j.freeradbiomed.2021.11.020
复制
发表时间：
2021-11
影响因子：
7.4
通讯作者：
Haidi Yang;Yafeng Zhu;Yongyi Ye;Jiao Guan;Xin Min;H. Xiong
中科院分区：
文献类型：
--
作者：
Haidi Yang;Yafeng Zhu;Yongyi Ye;Jiao Guan;Xin Min;H. Xiong
Nitric oxide (NO) is critically involved in the regulation of a wide variety of physiological and pathophysiological processes. However, the role of NO in the pathogenesis of noise-induced hearing loss (NIHL) is complex and remains controversial. Here we reported that treatment of CBA/J mice withl-arginine, a physiological precursor of NO, significantly reduced noise-induced reactive oxygen species accumulation in outer hair cells (OHCs), attenuated noise-induced loss of OHCs and NIHL consequently. Conversely, pharmacological inhibition of endothelial nitric oxide synthase exacerbated noise-induced loss of OHCs and aggravated NIHL. In HEI-OC1 cells, NO also showed substantial protection against H2O2-induced oxidative stress and cytotoxicity. Mechanistically, NO increased S-nitrosylation of pyruvate kinase M2 (PKM2) and inhibited its activity, which thus diverted glucose metabolic flux from glycolysis into the pentose phosphate pathway to increase production of reducing equivalents (NADPH and GSH) and eventually prevented H2O2-induced oxidative damage. These findings open new avenues for protection of cochlear hair cells from oxidative stress and prevention of NIHL through NO modulation of PKM2 and glucose metabolism reprogramming.
