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Toxicology Commons

Open Access. Powered by Scholars. Published by Universities.®

2012

Autophagosome, Autophagy, Cationic amphiphilic drugs, Cytoskeleton, Niemann Pick Type C, Trafficking

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Full-Text Articles in Toxicology

Cationic Amphiphilic Drug-Induced Autophagosome Accumulation Is Due To Autophagosome Sequestration Within Vimentin Intermediate Filament Networks Resulting In Prolonged Autophagosome Half-Life, Miriam Devorah Kleinman Jan 2012

Cationic Amphiphilic Drug-Induced Autophagosome Accumulation Is Due To Autophagosome Sequestration Within Vimentin Intermediate Filament Networks Resulting In Prolonged Autophagosome Half-Life, Miriam Devorah Kleinman

Wayne State University Dissertations

Accumulations of autophagosomes and non-esterified cholesterol are

observed in several cell lines derived from lysosomal storage diseases,

including Niemann Pick Type C (NPC). The relationship between

autophagosome accumulation and lysosomal non-esterified cholesterol is

unclear. Exposure of murine hepatoma 1c1c7 cultures to the cationic

amphiphilic drugs (CADs) U18666A, imipramine and clozapine caused

lysosomal non-esterified cholesterol and autophagosome accumulation.

Measurement of LC3-II conversion in the presence of lysosomal inhibitors

bafilomycin A1 and NH4Cl, degradation of long-lived proteins, and

colocalization of GFP-LC3 and LAMP1 indicated an increase in

autophagosome synthesis without compensatory increase in clearance.

Autophagosome synthesis was blocked using 3-MA to monitor …