Ultralstructural and biochemical studies of the effect of polychlorinated biphenyl on mouse parotid gland cells

Kawasaki, Goro; Mataki, Shiro; Mizuno, Akio

doi:10.1016/0003-9969(94)00145-2

Cited by 6 publications

(1 citation statement)

References 13 publications

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“…Their work, for the first time, reports the association of PCB exposure with autophagy. However, PCB exposure was previously reported to change the ultrastructure of cells, such as alterations of mitochondrial morphology, vacuolization of the cytoplasm, deformation/swollen nuclei, and increased activity of lysosomal enzymes, which also provided signs of deregulated autophagy. − Because of growing evidence on the toxic contribution of PCB metabolites, we investigated the autophagic effect of an active quinone-type metabolite, and the results showed that the exposure of HepG2 and MDA-MB-231 cells to PCB29-pQ causes morphological changes and autophagic-related gene alterations indicative of autophagy.…”

Section: Discussionmentioning

confidence: 99%

Quinones Derived from Polychlorinated Biphenyls Induce ROS-Dependent Autophagy by Evoking an Autophagic Flux and Inhibition of mTOR/p70S6k

Shi

Song

Liu

et al. 2016

Chem. Res. Toxicol.

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Autophagy is a "self-eating" destructive process that eliminates damaged organelles to maintain cellular homeostasis. Polychlorinated biphenyls (PCBs) are one of the most infamous industrial pollutants, which are ubiquitous in nature. In the present study, we found that an active, quinone-type PCB metabolite (PCB29-pQ) treatment causes an autophagic response through mTOR/p70S6k inhibition in HepG2 and MDA-MB-231 cells. Furthermore, our data suggested that PCB29-pQ enhances autophagosome formation through autophagic vacuole (AV) biogenesis, which evokes autophagic flux and induces AV-lysosome colocalization. The inhibition of autophagy enhanced PCB29-pQ-caused cytotoxicity, suggesting that autophagy serves as pro-survival machinery that plays a protective role in the early stage of PCB29-pQ-induced insult. However, higher concentration of PCB29-pQ exposure (>5 μM) caused autophagic cell death, which implied a shift from "pro-survival" to "pro-death" upon autophagic signaling. N-Acetylcysteine suppressed PCB29-pQ-induced autophagy and cytotoxicity, suggesting that ROS plays an important role in the regulation of PCB29-pQ-induced autophagy. Because autophagy shows significant implications in various human diseases and conditions, our current study provides a new mechanism for PCB-associated toxicity.

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Section: Discussionmentioning

confidence: 99%

Quinones Derived from Polychlorinated Biphenyls Induce ROS-Dependent Autophagy by Evoking an Autophagic Flux and Inhibition of mTOR/p70S6k

Shi

Song

Liu

et al. 2016

Chem. Res. Toxicol.

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Select microtubule inhibitors increase lysosome acidity and promote lysosomal disruption in acute myeloid leukemia (AML) cells

et al. 2015

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To identify new biological vulnerabilities in acute myeloid leukemia, we screened a library of natural products for compounds cytotoxic to TEX leukemia cells. This screen identified the novel small molecule Deoxysappanone B 7,4' dimethyl ether (Deox B 7,4), which possessed nanomolar anti-leukemic activity. To determine the anti-leukemic mechanism of action of Deox B 7,4, we conducted a genome-wide screen in Saccharomyces cerevisiae and identified enrichment of genes related to mitotic cell cycle as well as vacuolar acidification, therefore pointing to microtubules and vacuolar (V)-ATPase as potential drug targets. Further investigations into the mechanisms of action of Deox B 7,4 and a related analogue revealed that these compounds were reversible microtubule inhibitors that bound near the colchicine site. In addition, Deox B 7,4 and its analogue increased lysosomal V-ATPase activity and lysosome acidity. The effects on microtubules and lysosomes were functionally important for the anti-leukemic effects of these drugs. The lysosomal effects were characteristic of select microtubule inhibitors as only the Deox compounds and nocodazole, but not colchicine, vinca alkaloids or paclitaxel, altered lysosome acidity and induced lysosomal disruption. Thus, our data highlight a new mechanism of action of select microtubule inhibitors on lysosomal function.

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Dental caries in Faroese children exposed to polychlorinated biphenyls

Jan¹,

Reinert²

2008

Environmental Toxicology and Pharmacology

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Ultralstructural and biochemical studies of the effect of polychlorinated biphenyl on mouse parotid gland cells

Cited by 6 publications

References 13 publications

Quinones Derived from Polychlorinated Biphenyls Induce ROS-Dependent Autophagy by Evoking an Autophagic Flux and Inhibition of mTOR/p70S6k

Quinones Derived from Polychlorinated Biphenyls Induce ROS-Dependent Autophagy by Evoking an Autophagic Flux and Inhibition of mTOR/p70S6k

Select microtubule inhibitors increase lysosome acidity and promote lysosomal disruption in acute myeloid leukemia (AML) cells

Dental caries in Faroese children exposed to polychlorinated biphenyls

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