RNA‐Seq identifies redox balance related gene expression alterations under acute cadmium exposure in yeast

Abstract

The nonessential metal cadmium can cause cell toxicity and is associated with a range of human diseases including cardiovascular diseases, neurodegenerative diseases and cancers. In this study, cadmium-induced global gene expression profile of yeast was obtained using RNA Sequencing (RNA-Seq) and further analyzed by means of informatics and experiments. A total of 912 Differentially Expressed Genes (DEGs) (FDR of q < 0.01), including 415 Cd-inducible and 497 Cd-repressed genes were identified. Based on the DEGs, 25 cadmium responsive Clusters of Orthologous Group (COG) and three types of cadmium-induced Gene Ontology (GO) including cellular components, molecular functions and biological processes were analyzed in details. Thereafter, 79 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways under cadmium exposure were assigned. Collectively, 108 redox balance related genes were extracted under cadmium exposure. Meanwhile, cadmium exposure lowered cellular Mitochondrial Membrane Potential (MMP) and increased Reactive Oxygen Species (ROS) levels significantly in the context of mitochondrial dysfunction. Furthermore, cadmium exposure increased cellular GSH levels and decreased GSSG levels and also lowered GSSG/GSH ratio of cells, which supports experimentally our claim that the redox balance is the primary mechanism for cadmium toxicity. The results present in this study may provide new strategies for cadmium detoxification and prevention or therapies of cadmium-associated diseases.

Altered Mediator dynamics during heat shock in budding yeast

“…We first tested the effect of CdCl2 exposure on Pol II association by ChIP-seq ( Figure 6A). Marked induction of Pol II association was observed with the 47 genes showing the largest increase in mRNA abundance upon CdCl2 exposure (Momose and Iwahashi 2001), while association of Pol II with RP genes decreased to near baseline levels, in agreement with previous studies showing suppression of RP gene mRNA species upon CdCl2 exposure (Momose and Iwahashi 2001;Hosiner et al 2014;Huang et al 2016). Promoters showing at least 3-fold increase in normalized Pol II occupancy upon CdCl2 administration, and from the top 1000 Pol II-occupied genes after CdCl2 exposure, overlapped strongly with those identified in microarray studies (data not shown) (Momose and Iwahashi 2001).…”

“…To this end, we chose to examine the effect of exposure to CdCl2. Exposure to this toxic metal at sub-millimolar concentrations induces a rapid transcriptional response in which ~150-500 genes are induced and from 18 to ~400 genes repressed (Momose and Iwahashi 2001;Cormier et al 2010;Hosiner et al 2014;Huang et al 2016). Induced genes are enriched for binding sites for Hsf1, Msn2, and Msn4, and genes involved in ribosomal biogenesis are repressed by CdCl2 exposure, in common with the response to heat shock and other environmental stresses (Gasch et al 2000;Causton et al 2001;Hosiner et al 2014).…”

“…Induced genes are enriched for binding sites for Hsf1, Msn2, and Msn4, and genes involved in ribosomal biogenesis are repressed by CdCl2 exposure, in common with the response to heat shock and other environmental stresses (Gasch et al 2000;Causton et al 2001;Hosiner et al 2014). However, CdCl2 exposure also induces genes involved in sulfur compound metabolism (particularly the MET genes), among others, that are not involved in the heat shock response (Momose and Iwahashi 2001;Cormier et al 2010;Hosiner et al 2014;Huang et al 2016), thus providing an environmental perturbation that results in a distinct but overlapping response to that elicited by heat shock.…”

Transcriptome Profile Alteration with Cadmium Selenide/Zinc Sulfide Quantum Dots in Saccharomyces cerevisiae

“…Their study revealed anti-oxidative genes ( GRX2 ) and redox homeostasis genes ( TRR1 , TRR2 , and TRX2 ) to be upregulated in response to CdCl 2 exposure, due to potential release of Cd 2+ ions [26]. Interestingly, cadmium is not redox-active, which means it cannot generate ROS directly, yet, Cd-induced ROS is a commonly observed response [27]. They pointed out that metals, such as As 3+ , Cd 2+ , and Hg 2+ , had an affinity toward thiol groups (-SH), which play disparate roles in the function of enzymes, transcription factors, and membrane proteins [26].…”

A Schiff Base Macrocycle Ligand and Its Mg(II) and Cd(II) Complexes: Spectral Properties with Theoretical Understanding and Biological Activity

“…Inspired with the above facts, here we have synthesized some macrocyclic complexes where the d 10 metal are introduced in the core lipophilic moiety, which can favour the loading of different healing agents and at the same time the availability of metal ions are also limited. The macrocyclic ligand was synthesized by Schiff base condensation reaction and further treated with two metal ions, a bio friendly main group metal ion Mg(II) and a biologically not so accepted transition metal ion Cd(II)–, to get the metal‐ macrocycle complexes (Scheme ). Mg(II) forms one complex, [L1 4– (Mg 2+ ) 2 ] ( 1 ) where Cd (II) forms a mixture of two non‐separable complexes, [L1 4– (Cd 2+ ) 2 (H 2 O) 2 ] ( 2 ) and [H 2 L1 2– Cd 2+ ] ( 3 ).…”