Escins Isolated from Aesculus chinensis Bge. Promote the Autophagic Degradation of Mutant Huntingtin and Inhibit its Induced Apoptosis in HT22 cells

Frontiers in Pharmacology
Yueshan SunJianming Wu

Abstract

The pathogenesis of Huntington's disease (HD), an inherited progressive neurodegenerative disease, is highly associated with the cytotoxicity-inducing mutant huntingtin (mHtt) protein. Emerging evidence indicates that autophagy plays a pivotal role in degrading aggregated proteins such as mHtt to enhance neuronal viability. In this study, by employing preparative high-performance liquid chromatography (pre-HPLC), ultra-high performance liquid chromatography diode-array-detector quadrupole time-of-flight mass spectrometry (UHPLC-DAD-Q-TOF-MS) and nuclear magnetic resonance (NMR), three escins, escin IA (EA), escin IB (EB) and isoescin IA (IEA), were isolated and identified from the seed of Aesculus chinensis Bge. (ACB). After EGFP-HTT74-overexpressing HT22 cells were treated with EA, EB and IEA at safe concentrations, the clearance of mHtt and mHtt-induced apoptosis were investigated by Western blot, immunofluorescence microscopy and flow cytometry methods. In addition, the autophagy induced by these escins in HT22 cells was monitored by detecting GFP-LC3 puncta, P62 and LC3 protein expression. The results showed that EA, EB and IEA could significantly decrease mHtt levels and inhibit its induced apoptosis in HT22 cells. In addi...Continue Reading

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Citations

Oct 17, 2020·Oxidative Medicine and Cellular Longevity·Xinjie GaoYuxiang Gu
Feb 5, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Bing Han, Chengwei He
Aug 10, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Wen-Qiao QiuAn-Guo Wu
Nov 7, 2021·Cellular and Molecular Life Sciences : CMLS·Rohan Gupta Pravir Kumar

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Methods Mentioned

BETA
chemical modifications
transfection
nuclear magnetic resonance
flow cytometry
fluorescence microscopy
total ion chromatography
NMR
transgenic

Software Mentioned

GraphPad
Peak View
ImageJ
FlowJo
GraphPad Prism

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