期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 510, 期 3, 页码 427-434出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2019.01.121
关键词
Vacuolin-1; siRNA; Lipid nanoparticle; Autophagy
资金
- NSFC [31500689]
- Shenzhen Science and Technology grant [J120170301]
- Innovation and Technology Fund grant [ITS/280/14]
Autophagy and endocytosis are important pathways regulating macromolecule recycling and regeneration. Small molecule inhibitors are utilized to modulate these pathways and to treat autophagy-related diseases. Vacuolin-1 is a small molecule that can potently and reversibly inhibit autophagy by activating Rab5. In addition, Vacuolin-1 can be applied to inhibit exocytosis in a variety of cell types. Here we report that Vacuolin-1 significantly reduces small interference RNA (siRNA)-mediated gene silencing delivered by liposome transfection reagent or lipid nanoparticles in Hela cells. Vacuolin-1 exhibits the strongest inhibition effect among a few autophagy inhibitors including Chloroquine, Wortmannin, and Bafilomycin A1. We found that siRNAs are over-accumulated intracellularly and colocalized with a late endosome marker Rab7 in Vacuolin-1 treated cells, suggesting Vacuolin-1 inhibits the cytoplasmic release of lipid siRNA complexes from late endosomes. We propose that Vacuolin-1 could potentially be used to control the effects of lipid nanoparticle-based RNAi and gene therapy drugs. (C) 2019 Elsevier Inc. All rights reserved.
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