Protection of melatonin against acidosis‐induced neuronal injuries

Autor: Xiao-Ming Wang, Can Yang, Zhi-Kang Cheng, Xin-Wen Zhou, Peng Zeng, Qun Wang, Qing Tian, Yan Shi, Ying-Yan Fang, Chao-Yuan Ye, Fu-Yuan Cao, Er-Li Cai
Rok vydání: 2020
Předmět:
Zdroj: Journal of Cellular and Molecular Medicine
ISSN: 1582-4934
1582-1838
DOI: 10.1111/jcmm.15351
Popis: Acidosis, a common feature of cerebral ischaemia and hypoxia, plays a key role in these pathological processes by aggravating the ischaemic and hypoxic injuries. To explore the mechanisms, in this research, we cultured primary neurons in an acidic environment (potential of hydrogen [pH]6.2, 24 hours) to mimic the acidosis. By proteomic analysis, 69 differentially expressed proteins in the acidic neurons were found, mainly related to stress and cell death, synaptic plasticity and gene transcription. And, the acidotic neurons developed obvious alterations including increased neuronal death, reduced dendritic length and complexity, reduced synaptic proteins, tau hyperphosphorylation, endoplasmic reticulum (ER) stress activation, abnormal lysosome‐related signals, imbalanced oxidative stress/anti‐oxidative stress and decreased Golgi matrix proteins. Then, melatonin (1 × 10−4 mol/L) was used to pre‐treat the cultured primary neurons before acidic treatment (pH6.2). The results showed that melatonin partially reversed the acidosis‐induced neuronal death, abnormal dendritic complexity, reductions of synaptic proteins, tau hyperphosphorylation and imbalance of kinase/phosphatase. In addition, acidosis related the activations of glycogen synthase kinase‐3β and nuclear factor‐κB signals, ER stress and Golgi stress, and the abnormal autophagy‐lysosome signals were completely reversed by melatonin. These data indicate that melatonin is beneficial for neurons against acidosis‐induced injuries.
Databáze: OpenAIRE
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