Abstract

Lipopolysaccharide, known as endotoxin, can stimulate potent host immune responses through the complex of Toll-like-receptor 4 and myeloid differentiation protein 2; but its influence on Saccharomyces cerevisiae, a model organism for studying eukaryotes, is not clear. In this study, we found that lipopolysaccharide-treated S. cerevisiae cells could be stained by methylene blue, but did not die. Transcriptional profiling of the lipopolysaccharide-treated S. cerevisiae cells showed that 5745 genes were modulated: 2491 genes up-regulated and 3254 genes down-regulated. Significantly regulated genes (460 up-regulated genes and 135 down-regulated genes) in lipopolysaccharide-treated S. cerevisiae cells were analyzed on Gene Ontology, and used to establish physical protein-protein interaction network and protein phosphorylation network. Based on these analyses, most of the regulated genes in lipopolysaccharide-treated S. cerevisiae cells were related to cell wall, membrane, peroxisome and mitochondrion. Further experiments demonstrated that lipopolysaccharide stimulation caused the exposure of phosphatidylserine and the increase of mitochondrial membrane potential in S. cerevisiae cells, but levels of intracellular reactive oxygen species and metacaspase activation were not increased. This study demonstrated that lipopolysaccharide stimulation causes significant changes in S. cerevisiae cells, and the results would contribute to understand the response of eukaryotic cells to lipopolysaccharide stimulation.

Highlights

  • Saccharomyces cerevisiae is a model organism commonly used to study many obscure aspects of important human pathologies that are harder to elucidate using other more complex eukaryotic models [1,2,3]

  • Lipopolysaccharide (LPS), known as endotoxin, is an essential component of the outer membrane in most Gram-negative bacteria, and it consists of a hydrophobic moiety termed as lipid A and a large polysaccharide subdivided into the nonrepeating ‘‘core’’ oligosaccharide and the O-antigen repeats [12,13]

  • The decreased DYm and increased reactive oxygen species (ROS) production in yeast were observed in response to aspirin, rapamycin, osmotin or formic acid [7,8,44,45]

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Summary

Introduction

Saccharomyces cerevisiae is a model organism commonly used to study many obscure aspects of important human pathologies that are harder to elucidate using other more complex eukaryotic models [1,2,3]. Different stresses cause different responses in S. cerevisiae and usually result in cell death [3,4]. Heat shock, oxidative stress and reagents such as formic acid and aspirin commit apoptosis in S. cerevisiae cells [5,6,7,8], while leucine starvation and the pharmacological reagent rapamycin cause autophagy [9,10,11]. As a pathogen-associated antigen, LPS can be recognized by different immune cells through a protein complex consisting of Toll-like receptor 4 and myeloid differentiation protein 2, trigger the production and release of pro-inflammatory cytokines, and activate the immune cells in inflammatory systems [14]. To understand the detailed mechanism on the response of S. cerevisiae to LPS, we systematically investigated LPS-treated S. cerevisiae BY4742 cells using transcriptome analysis and different staining methods

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