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Combining autophagy-inducing peptides and Brefeldin A delivered by perinuclear-localized mesoporous silica nanoparticles: a manipulation strategy for ER-phagy

Abstract

Autophagic degradation of endoplasmic reticulum (ER-phagy) has been found to play a critical role in human sensory neuropathy. So far, however, specific and efficient intervention means for ER-phagy remains unexplored. Herein, Brefeldin A (BFA), a blocking agent on protein transport between ER and Golgi, was screened from ER stress inducers. BFA was then delivered to the perinuclear area co-localized with ER by mesoporous silica nanoparticles based drug-carrier functionalized with autophagy-inducing peptides of TAT-Beclin 1 (MSNs-BFA), to evoke a perturbation of ER-phagy. The molecular mechanism of ER-phagy regulated by BFA was explored by biochemical evaluation including time-lapse live-cell fluorescence imaging. We found that MSNs-BFA treatment caused a lower mRNA/protein expression level of FAM134b even under a compensation of autophagic flux in U2OS cells, and resulted in ER-expansion. The fragmentation of ER was blocked as a response to ER stress mediated by inactivation of AKT/TSC/mTOR pathway. Our work developed an efficient external manipulation strategy to regulate ER-phagy and may contribute to therapeutic application of autophagy-related major human diseases.

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Publication details

The article was received on 31 Jan 2018, accepted on 05 Apr 2018 and first published on 11 Apr 2018


Article type: Paper
DOI: 10.1039/C8NR00872H
Citation: Nanoscale, 2018, Accepted Manuscript
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    Combining autophagy-inducing peptides and Brefeldin A delivered by perinuclear-localized mesoporous silica nanoparticles: a manipulation strategy for ER-phagy

    Y. Wang, Z. Zhao, F. Wei, Z. Luo and Y. Duan, Nanoscale, 2018, Accepted Manuscript , DOI: 10.1039/C8NR00872H

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