自噬
螺旋神经节
神经毒性
二甲双胍
神经保护
化学
细胞生物学
变性(医学)
药理学
内科学
内分泌学
生物
细胞凋亡
医学
神经科学
生物化学
毒性
糖尿病
病理
耳蜗
有机化学
作者
Qian Li,Liuqian Wang,Di Ji,Wei Yu,Yan Zhang,Xiang Yanghong,Chao Zhou,Liting Wang,Ping Deng,Huifeng Pi,Yonghui Lu,Qinlong Ma,Mindi He,Lei Zhang,Zhengping Yu,An-chun Deng
标识
DOI:10.1016/j.jinorgbio.2022.111901
摘要
Cadmium (Cd), a common environmental and occupational toxicant, is an important risk factor for hearing loss. After exposure, Cd accumulates in the inner ear and induces spiral ganglion neuron (SGN) degeneration; however, the underlying mechanisms are poorly understood. Dysfunctional autophagy has been implicated in many neurodegenerative diseases, including Cd-induced neurotoxicity. Metformin has been validated to confer not only anti-hyperglycaemic but also neuroprotective effects. However, the relationship between autophagy dysfunction, SGN degeneration, and the effect of metformin on Cd-induced SGN neurotoxicity has not yet been established. In this study, we demonstrate that metformin notably attenuates Cd-evoked SGN degeneration by restoring impaired autophagy flux, as evidenced by the suppression of Cd-induced elevation of autophagy markers microtubule-associated protein 1A/1B-light chain 3-II (LC3-II) and autophagy substrate protein p62 in degenerated SGN. Blockage of autophagy flux by chloroquine abolished metformin-induced neuroprotection against Cd-induced neurotoxicity in SGN. The results of this study reveal that autophagy dysfunction is an important component of Cd-induced SGN degeneration, and metformin may be a potential protective agent for attenuating SGN degeneration following Cd exposure.
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