NADPH oxidase inhibitor apocynin decreases mitochondrial dysfunction and apoptosis in the ventral cochlear nucleus of D-galactose-induced aging model in rats
NADPH oxidase inhibitor apocynin decreases mitochondrial dysfunction and apoptosis in the ventral cochlear nucleus of D-galactose-induced aging model in rats
复制标题
NADPH 氧化酶抑制剂罗布麻素可降低 D-半乳糖诱导的衰老模型大鼠耳蜗腹侧核线粒体功能障碍和细胞凋亡
DOI：
10.1016/j.neuint.2018.12.008
复制
发表时间：
2019-03-01
影响因子：
4.2
通讯作者：
Gong, Shu-Sheng
中科院分区：
文献类型：
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作者：
Du, Zheng-De;Yu, Shukui;Gong, Shu-Sheng
老年性耳聋已成为人类常见的感觉缺陷。线粒体DNA的氧化损伤和线粒体功能障碍与听觉系统的衰老密切相关。以前的研究用D-半乳糖（D-gal）建立了模拟衰老的大鼠模型，并首次报道了耳蜗腹侧核（VCN）内NADPH氧化酶依赖的线粒体氧化损伤和凋亡可能参与了D-gal诱导的中枢性老年性聋。在这项研究中，我们研究了夹竹桃素，NADPH氧化酶抑制剂，对线粒体功能障碍和细胞凋亡的依赖性细胞凋亡的D-gal诱导的衰老模型大鼠的VCN。我们的数据表明，夹竹桃麻素降低NADPH氧化酶活性，H2 O2水平，线粒体DNA共同缺失，8-羟基-2-脱氧鸟苷（8-OHdG）的表达和增加总超氧化物歧化酶（T-SOD）和谷胱甘肽过氧化物酶（GSH-Px）的活性在D-gal诱导的衰老模型大鼠的VCN。此外，夹竹桃麻素还降低了D-半乳糖诱导的衰老模型大鼠VCN中磷酸化p47（phox）（p-p47（phox））、肿瘤坏死因子α（TNF α）和解偶联蛋白2（UCP 2）的蛋白水平。夹竹桃麻素能减轻D-半乳糖致衰老大鼠VCN线粒体超微结构损伤，增加ATP生成和线粒体膜电位（MMP）水平。此外，夹竹桃麻素抑制细胞色素c（Cyt c）从线粒体到细胞质的易位，抑制caspase 3依赖的细胞凋亡在D-半乳糖诱导的大鼠VCN衰老模型。因此，我们的研究结果表明，NADPH氧化酶抑制剂促进神经元的存活是一种潜在的有效方法，以提高神经元的抗中枢性老年性聋。
Presbycusis has become a common sensory deficit in humans. Oxidative damage to mitochondrial DNA and mitochondrial dysfunction is strongly associated with the aging of the auditory system. A previous study established a mimetic rat model of aging using D-galactose (D-gal) and first reported that NADPH oxidase-dependent mitochondria] oxidative damage and apoptosis in the ventral cochlear nucleus (VCN) might contribute to D-gal-induced central presbycusis. In this study, we investigated the effects of apocynin, an NADPH oxidase inhibitor, on mitochondrial dysfunction and mitochondria-dependent apoptosis in the VCN of D-gal-induced aging model in rats. Our data showed that apocynin decreased NADPH oxidase activity, H2O2 levels, mitochondrial DNA common deletion, and 8-hydroxy-2-deoxyguanosine (8-OHdG) expression and increased total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activity in the VCN of D-gal-induced aging model in rats. Moreover, apocynin also decreased the protein levels of phospho-p47(phox)(p-p47(phox)), tumor necrosis factor alpha (TNF alpha), and uncoupling protein 2 (UCP2) in the VCN of D-gal-induced aging model in rats. Meanwhile, apocynin alleviated mitochondrial ultrastructure damage and enhanced ATP production and mitochondrial membrane potential (MMP) levels in the VCN of D-gal-induced aging model in rats. Furthermore, apocynin inhibited cytochrome c (Cyt c) translocation from mitochondria to the cytoplasm and suppressed caspase 3-dependent apoptosis in the VCN of D-gal-induced aging model in rats. Consequently, our findings suggest that neuronal survival promoted by an NADPH oxidase inhibitor is a potentially effective method to enhance the resistance of neurons to central presbycusis.