Celastrol attenuates ischemia/reperfusion-mediated memory dysfunction by downregulating AK005401/MAP3K12.

Oxidative stress induces mitochondrial dysfunction, causing memory loss. Long noncoding RNAs influence mitochondrial function and suppress oxidative stress by regulating target protein expression and gene transcription. Celastrol, a natural antioxidant extracted from Tripterygium wilfordii Hook F. ("Thunder of God Vine"), effectively alleviates oxidative stress-mediated tissue injury. In the present study, we examined the effects of celastrol on memory dysfunction induced by ischemia/reperfusion (I/R) and elucidated the mechanisms underlying these effects. C57BL/6 mice were used to mimic I/R using the bilateral common carotid clip reperfusion method, and a hippocampal cell line (HT-22) cells were used to establish a model of oxygen-glucose deprivation/reoxygenation (OGD/R). We observed changes in behavior and mitochondrial structure. Cell activity, cell respiration, and antioxidant capacity were measured. MAP3K12, p-JNK, p-c-Jun, p-Akt/Akt, PI3K, Bcl-2, and Bax expression were evaluated. I/R or OGD/R significantly increased AK005401 and MAP3K12 expression, further attenuating PI3K/Akt activation, promoting reactive oxygen species generation and causing mitochondrial dysfunction and cell apoptosis, thereby resulting in memory dysfunction. Celastrol increased antioxidant capacity, inhibited cell apoptosis, and improved mitochondrial function, effectively improving learning and memory by downregulating AK005401 and MAP3K12 and activating PI3K/Akt. The AK005401/MAP3K12 signaling pathway has an important role in I/R-mediated hippocampal injury, and celastrol can potentially reduce or possibly prevent I/R-induced neuronal injury by downregulating AK005401/MAP3K12 signaling. Copyright © 2020. Published by Elsevier GmbH.

Citation

Chaoyun Wang, Hongzhi Wan, Miao Li, Chunxiang Zhang. Celastrol attenuates ischemia/reperfusion-mediated memory dysfunction by downregulating AK005401/MAP3K12. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2021 Feb;82:153441

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PMID: 33387968

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