Arsenic induces mTOR-dependent autophagy, whereas it impairs the autophagy-lysosome pathway and the potential role of TFEB in cultured dendritic cells.

Metallomics : Integrated Biometal Science
Lu ZhaoBing Li

Abstract

Arsenic is a toxic metalloid, which also compromises immunity and causes various immunological disorders. Exposure to arsenic exerts the immunosuppressive properties of dendritic cells (DCs). Autophagy is a self-renewal process of cells, which degrades damaged macromolecules and organelles through the lysosomal pathway. Thus, herein, we attempt to clarify the impacts of autophagy and the autophagy-lysosome pathway on arsenic-exposed DCs. Bone marrow-derived dendritic cells (BMDCs) were exposed to different concentrations of arsenic (0.25, 0.5 and 1 μM) with or without LPS stimulation. Initially, we observed that arsenic induced autophagosome accumulation, significantly enhanced the LC3 II and p62 expressions and down-regulated the p-mTOR protein levels. We also determined that arsenic-induced autophagy occurred via an mTOR pathway. The results further revealed that arsenic inhibited autophagic flux in LPS-stimulated BMDCs using the autophagy inhibitor chloroquine (CQ). Meanwhile, arsenic significantly decreased the number of lysosomes, protein expression of lysosomal-specific markers LAMP1 and LAMP2, and the protein levels of lysosomal cysteine cathepsins (CTSD and CTSL). Moreover, the overexpression of transcription factor EB ...Continue Reading

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Citations

Aug 23, 2020·Journal of Clinical Medicine·Alain CalenderYves Pacheco
Jan 31, 2021·Environmental Science and Pollution Research International·Hangjun ZhangYuchi Zhong
Dec 15, 2020·Metallomics : Integrated Biometal Science·Irene BarguillaAlba Hernández

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Methods Mentioned

BETA
transfection
protein assay
electrophoresis
PCR
fluorescence microscopy
transmission electron microscopy
ELISA
enzyme-linked immunosorbent assay

Software Mentioned

Prism
QuantStudio
SPSS
GraphPad

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