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Zinc oxide nanoparticles induce toxicity by affecting cell wall integrity pathway, mitochondrial function and lipid homeostasis in Saccharomyces cerevisiae.

Abstract：

:Growing numbers of nanotoxicity research demonstrating that mechanical damage and oxidative stress are potential modes of nanoparticles (NPs) induced toxicity. However, the underlying mechanisms by which NPs interact with the eukaryotic cell and affect their physiological and metabolic functions are not fully known. We investigated the toxic effects of zinc oxide nanoparticles (ZnO-NPs) on budding yeast, Saccharomyces cerevisiae and elucidated the underlying mechanism. We observed cell wall damage and accumulation of reactive oxygen species (ROS) leading to cell death upon ZnO-NPs exposure. We detected a significant change in the cellular distribution of lipid biosynthetic enzymes (Fas1 and Fas2). Furthermore, exposure of ZnO-NPs altered the architecture of endoplasmic reticulum (ER) and mitochondria as well as ER-mitochondria encounter structure (ERMES) complex causing cellular toxicity due to lipid disequilibrium and proteostasis. We also observed significant changes in heat shock and unfolded protein responses, monitored by Hsp104-GFP localization and cytosolic Hac1 splicing respectively. Moreover, we observed activation of MAP kinases of CWI (Mpk1) and HOG (Hog1) pathways upon exposure to ZnO-NPs. Transcript level analyses showed induction of chitin synthesis and redox homeostasis genes. Finally, we observed induction in lipid droplets (LDs) formation, distorted vacuolar morphology and induction of autophagy as monitored by localization of Atg8p. However, we did not observe any significant change in epigenetic marks, examined by western blotting. Altogether, we provide evidence that exposure of ZnO-NPs results in cell death by affecting cell wall integrity and ER homeostasis as well as accumulation of ROS and saturated free fatty acids.

journal_name

Chemosphere

journal_title

Chemosphere

authors

Babele PK,Thakre PK,Kumawat R,Tomar RS

doi

10.1016/j.chemosphere.2018.09.028

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

65-75

eissn

0045-6535

issn

1879-1298

pii

S0045-6535(18)31681-3

journal_volume

213

pub_type

杂志文章

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