Journal
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
Volume 228, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ecoenv.2021.112993
Keywords
Cadmium; Microtubule; Endosome; Lysosome; Kinesin-1; Autophagic flux
Categories
Funding
- National Key Research and Development Program of China [2016YFD0501208]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
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Cadmium exposure damages the microtubule network in BRL 3 A cells, leading to enlargement of endosome-lysosomes and blockage of autophagic flux. Kinesin-1, specifically KIF5B, plays a critical role in this process.
Acute exposure to cadmium (Cd) causes vacuolar degeneration in buffalo rat liver 3 A (BRL 3 A) cells. The present study aimed to determine the relationship between Cd-induced microtubule damage and intracellular vacuolar degeneration. Western blotting results showed that Cd damaged the microtubule network and downregulated the expression of microtubule-associated proteins-kinesin-1 heavy chain (KIF5B), gamma-tubulin, and acetylated alpha-tubulin in BRL 3 A cells. Immunofluorescence staining revealed that Cd inhibited interactions between alpha-tubulin and microtubule-associated protein 4 (MAP4) as well as KIF5B. Increasing Cd concentrations decreased the levels of the lipid kinase, PIKfyve, which regulates the activity of endosome-lysosome fission. Immunofluorescence and transmission electron microscopy revealed vacuole-like organelles that were late endosomes and lysosomes. The PIKfyve inhibitor, YM201636, and the microtubule depolymerizer, nocodazole, aggravated Cd-induced endosome-lysosome enlargement. Knocking down the kif5b gene that encodes KIF5B intensified the enlargement of endosome-lysosomes and expression of early endosome antigen 1 (EEA1), Rasrelated protein Rab-7a (RAB7), and lysosome-associated membrane glycoprotein 2 (LAMP2). Nocodazole, YM201636, and the knockdown of kif5b blocked autophagic flux. We concluded that Cd-induced damage to the microtubule network is the main reason for endosome-lysosome enlargement and autophagic flux blockage in BRL 3 A cells, and kinesin-1 plays a critical role in this process.
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