Cadmium induces endosomal/lysosomal enlargement and blocks autophagy flux in rat hepatocytes by damaging microtubules

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 n...

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Autores principales:	Junzhao Yuan, Yumeng Zhao, Yuni Bai, Jianhong Gu, Yan Yuan, Xuezhong Liu, Zongping Liu, Hui Zou, Jianchun Bian
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Cadmium Microtubule Endosome Lysosome Kinesin-1 Autophagic flux Environmental pollution TD172-193.5 Environmental sciences GE1-350
Acceso en línea:	https://doaj.org/article/5ba97bc63167488a88aa4df8540a6e61
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spelling	oai:doaj.org-article:5ba97bc63167488a88aa4df8540a6e612021-11-20T04:55:37ZCadmium induces endosomal/lysosomal enlargement and blocks autophagy flux in rat hepatocytes by damaging microtubules0147-651310.1016/j.ecoenv.2021.112993https://doaj.org/article/5ba97bc63167488a88aa4df8540a6e612021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0147651321011052https://doaj.org/toc/0147-6513Acute 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), γ-tubulin, and acetylated α-tubulin in BRL 3 A cells. Immunofluorescence staining revealed that Cd inhibited interactions between α-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), Ras-related 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.Junzhao YuanYumeng ZhaoYuni BaiJianhong GuYan YuanXuezhong LiuZongping LiuHui ZouJianchun BianElsevierarticleCadmiumMicrotubuleEndosomeLysosomeKinesin-1Autophagic fluxEnvironmental pollutionTD172-193.5Environmental sciencesGE1-350ENEcotoxicology and Environmental Safety, Vol 228, Iss , Pp 112993- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cadmium Microtubule Endosome Lysosome Kinesin-1 Autophagic flux Environmental pollution TD172-193.5 Environmental sciences GE1-350
spellingShingle	Cadmium Microtubule Endosome Lysosome Kinesin-1 Autophagic flux Environmental pollution TD172-193.5 Environmental sciences GE1-350 Junzhao Yuan Yumeng Zhao Yuni Bai Jianhong Gu Yan Yuan Xuezhong Liu Zongping Liu Hui Zou Jianchun Bian Cadmium induces endosomal/lysosomal enlargement and blocks autophagy flux in rat hepatocytes by damaging microtubules
description	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), γ-tubulin, and acetylated α-tubulin in BRL 3 A cells. Immunofluorescence staining revealed that Cd inhibited interactions between α-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), Ras-related 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.
format	article
author	Junzhao Yuan Yumeng Zhao Yuni Bai Jianhong Gu Yan Yuan Xuezhong Liu Zongping Liu Hui Zou Jianchun Bian
author_facet	Junzhao Yuan Yumeng Zhao Yuni Bai Jianhong Gu Yan Yuan Xuezhong Liu Zongping Liu Hui Zou Jianchun Bian
author_sort	Junzhao Yuan
title	Cadmium induces endosomal/lysosomal enlargement and blocks autophagy flux in rat hepatocytes by damaging microtubules
title_short	Cadmium induces endosomal/lysosomal enlargement and blocks autophagy flux in rat hepatocytes by damaging microtubules
title_full	Cadmium induces endosomal/lysosomal enlargement and blocks autophagy flux in rat hepatocytes by damaging microtubules
title_fullStr	Cadmium induces endosomal/lysosomal enlargement and blocks autophagy flux in rat hepatocytes by damaging microtubules
title_full_unstemmed	Cadmium induces endosomal/lysosomal enlargement and blocks autophagy flux in rat hepatocytes by damaging microtubules
title_sort	cadmium induces endosomal/lysosomal enlargement and blocks autophagy flux in rat hepatocytes by damaging microtubules
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/5ba97bc63167488a88aa4df8540a6e61
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Cadmium induces endosomal/lysosomal enlargement and blocks autophagy flux in rat hepatocytes by damaging microtubules

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