Back to Search
Start Over
Genetic analysis of oxidative and endoplasmic reticulum stress responses induced by cobalt toxicity in budding yeast.
- Source :
-
Biochimica et biophysica acta. General subjects [Biochim Biophys Acta Gen Subj] 2020 Mar; Vol. 1864 (3), pp. 129516. Date of Electronic Publication: 2020 Jan 03. - Publication Year :
- 2020
-
Abstract
- Background: Cobalt is an important metal cofactor of many living cells. However, excessive cobalt is toxic and can cause cell death and even several diseases in humans. Saccharomyces cerevisiae is a useful tool for studying metal homeostasis and many of the genes and pathways are highly conserved in higher eukaryotes including humans.<br />Methods: The intracellular cobalt and reactive oxygen species (ROS) levels were measured by an atomic absorption spectrometer and DHE staining method, respectively. The expression of genes involved in scavenging oxidative stress was tested by qPCR method, while the expression of UPRE-lacZ report gene was analyzed via β-galactosidase activity assay.<br />Results: Using a genome-scale genetic screen, 153 cobalt-sensitive and 37 cobalt-tolerant gene deletion mutants were identified from Saccharomyces cerevisiae. We showed that 101 of the cobalt-sensitive mutants accumulated higher intracellular cobalt compared to wild-type. The intracellular ROS levels in 112 of the mutants were induced by cobalt, which might be caused by the decreased expression of genes involved in scavenging oxidative stress in response to cobalt. Moreover, more than one-third of the cobalt-sensitive mutants were also sensitive to tunicamycin, and cobalt stress might induce the unfolded protein response (UPR) through serine/threonine kinase and endoribonuclease Ire1.<br />Conclusions: This study reinforced the fact that cobalt toxicity might be due to the high intracellular cobalt and ROS levels, and the endoplasmic reticulum stress responses induced by cobalt.<br />General Significance: Elucidating the toxicity mechanisms of cobalt stress response will help reveal new routes for the treatment of the diseases induced by cobalt.<br /> (Copyright © 2020. Published by Elsevier B.V.)
- Subjects :
- Endoplasmic Reticulum metabolism
Endoplasmic Reticulum Stress physiology
Gene Expression Profiling methods
Homeostasis physiology
Oxidative Stress genetics
Protein Serine-Threonine Kinases genetics
Reactive Oxygen Species metabolism
Saccharomyces cerevisiae genetics
Saccharomyces cerevisiae metabolism
Saccharomyces cerevisiae Proteins genetics
Saccharomyces cerevisiae Proteins metabolism
Signal Transduction physiology
Spectrophotometry, Atomic methods
Unfolded Protein Response
Cobalt metabolism
Cobalt toxicity
Oxidative Stress physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1872-8006
- Volume :
- 1864
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta. General subjects
- Publication Type :
- Academic Journal
- Accession number :
- 31904504
- Full Text :
- https://doi.org/10.1016/j.bbagen.2020.129516