Arsenic metalloid is a double-edge sword. On the one hand it is a very toxic and powerful carcinogen, and on the other it has been successfully used in the treatment of acute promyelocytic leukemia. In order to prevent the deleterious effects caused by arsenic compounds, almost all living organisms have developed mechanisms to eliminate it. In this study genome-wide response of S. cerevisiae to arsenic shows that this metal interferes with genes involved in the iron homeostasis including those encoding proteins that function in iron uptake, incorporation into FeS clusters, and more. In addition our data indicate that Yap1 transcriptionally controls the iron homeostasis regulator AFT2 as well as its direct target, MRS4. Most importantly in response to arsenate exposure Yap1 strongly regulates the expression of several genes involved in the Fe-S proteins biosynthesis, namely NBP35 and YFH1. Interestingly mRNA levels encoding Fet3, Ferro-O2-oxidoreductase required for high-affinity iron uptake, are drastically destabilized upon arsenic exposure. Such destabilization is due to the 5 to 3 exonuclease Xrn1 localized in the P Bodies. Moreover FET3 mRNA decay is not mediated by Cth2 and is independent on the formation of ROS responsible for the toxic effects of arsenic compounds. Strikingly, in presence of arsenate fet3 mutant shows resistance over the wild-type which leads us to suggest that Fet3 has a role in arsenic toxicity. Unexpectedly arsenic treatment seems to activate the non-reductive iron uptake in order to maintain the cellular iron homeostasis. Furthermore our genetic, biochemical, and physiological analysis demonstrate that aft1 mutant is sensitive to arsenic compounds and such phenotype is reversible upon addition of iron. We also show that arsenic exposure induces iron deficiency in aft1 mutant. In conclusion this work shows for the first time that arsenic, a chemotherapy drug used to treat a specific type of acute promyelocytic leukemia (APL), disrupts iron homeostasis and our results suggest that this disruption is independent on ROS generation. Finally we provide preliminary data confirming that such disruption also takes place in mammalian cells, an observation that can be very relevant in term of clinical applications.
Arsenic stress elicits cytosolic Ca(2+) bursts and Crz1 activation in Saccharomyces cerevisiae.
Time
View SamplesWe recently reported that carbon monoxide (CO) has bactericidal activity. To understand its mode of action we analysed the gene expression changes occurring when Escherichia coli, grown aerobically and anaerobically, is treated with the carbon monoxide releasing molecule, CORM-2. The E. coli microarray analysis shows that E. coli CORM-2 response is multifaceted with a high number of differentially regulated genes spread through several functional categories, namely genes involved in inorganic ion transport and metabolism, regulators, and genes implicated in posttranslational modification, such as chaperones. CORM-2 has higher impact in E. coli cells grown anaerobically, as judged by the existence of repressed genes belonging to eight functional classes which are absent in aerobically CORM-2 treated cells. In spite of the relatively stable nature of the CO molecule, our results show that CO is able to trigger a significant alteration in the transcriptome of E. coli which necessarily has effects in several key metabolic pathways.
Exploring the antimicrobial action of a carbon monoxide-releasing compound through whole-genome transcription profiling of Escherichia coli.
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View SamplesBacteria are extremely versatile organisms which rapidly adapt to changing environments. When Escherichia coli cells switch from planktonic growth to biofilm, flagellum formation is turned off, and the production of fimbriae and extracellular polysaccharides is switched on. Here we show that BolA protein is a new bacterial transcription factor which modulates the switch from planktonic to sessile lifestyle. BolA negatively modulates flagella biosynthesis and thus swimming capacity. Furthermore, BolA overexpression favors biofilm formation and involvesinvolving fimbriae-like adhesins and curli production. Our results unraveled for the first time that BolA is a protein with high affinity to DNA, involved in the regulation of several genes of E. coli at a genome-wide scale level. Moreover, this observation further demonstrated that the most significant targets of this protein involved a complex network of genes encoding proteins extremely necessary in biofilm development processes. Herein we propose that BolA is a motile/adhesive transcriptional switch, specifically involved in the transition between the planktonic and the attachment stage of biofilm formation process.
BolA is a transcriptional switch that turns off motility and turns on biofilm development.
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View SamplesA toxicogenomic analysis from liver of different pharmacological active coumarins (mammea A/BA+A/BB 3:1 and soulatrolide ) was performed on mice treated (20mg/kg/daily) for a whole week to evaluate if such compounds possess or could develop a hazardous profile on liver.
Toxicogenomic analysis of pharmacological active coumarins isolated from Calophyllum brasiliense.
Sex, Specimen part, Treatment
View SamplesIn the present study, we have investigated the effect of CpG Oligodeoxynucleotides (CpG-ODN) on the outcome of Plasmodium infection of the mosquito vectors Anopheles stephensi and Anopheles gambiae and on the modulation of mosquito immunity to Plasmodium. Anopheles mosquitoes inoculated with CpG-ODN showed significant reduction of Plasmodium infection rate and intensity. Microarrays were used to profile transcription of fat-body from CpG-ODN-treated mosquitoes. Mosquitoes were dissected 18h after ODN inoculation (immediately before feeding). Batches of 20 to 30 fat bodies (abdomen without midgut, ovaries and malpighian tubule]) were dissected in cold DEPC-treated phosphate-buffered saline (PBS) and processed for RNA preparation. Mosquitoes treated with CpG-ODNs are less susceptible to Plasmodium infection. Transcription profile of fat body indicates that protection was associated with coagulation/wound healing, while melanization appears to be depressed.
CpG-containing oligodeoxynucleotides increases resistance of Anopheles mosquitoes to Plasmodium infection.
Sex, Specimen part, Treatment
View SamplesStalk borers are major pests for some of the most important crops in the world, such as maize or rice. Plant defense mechanisms against these herbivores have been poorly investigated. The maizes stalk responds to insect feeding activating defense genes including hormone biosynthetic-related or proteinase inhibitor transcripts. The most outstanding conclusion is that cells in the maizes stalk undergo cell wall fortification after corn borer tunneling.
Inducible maize defense mechanisms against the corn borer Sesamia nonagrioides: a transcriptome and biochemical approach.
Specimen part
View SamplesThe maize inbred line A661 shows a characteristic phenotype when grown at suboptimal temperatures for three weeks and then is exposed to optimal temperatures for one extra week. After this period the third leaf showed two well defined sections: distal (chlorophyll-less; CL) and proximal (chlorophyll-containing; CC) sections. To further investigate the performance of the inbred line A661 under cold conditions a gene expression profiling analysis was conducted using large scale maize microarrays. A total of 1002 transcripts change their expression between both leaf sections and the majority of these codify for proteins located to the chloroplast.
Genetic regulation of cold-induced albinism in the maize inbred line A661.
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View SamplesThe murine thymus produces discrete T cell subsets making either IFN- or IL-17, but the role of the TCR in this developmental process remains controversial. Here we generated a non-transgenic and polyclonal model of reduced TCR expression and signal strength selectively on T cells. Mice haploinsufficient for both CD3 and CD3 (CD3DH) showed normal thymocyte subsets but specific defects in T cell development, namely impaired differentiation of IL-17-producing embryonic V6+ (but not adult V4+) T cells and a marked depletion of IFN--producing CD122+ NK1.1+ (V1-biased) T cells throughout life. As result, adult CD3DH mice showed defective peripheral IFN- responses and were resistant to experimental cerebral malaria. Thus, strong TCR signaling is required within specific developmental windows with distinct V usage and differential cytokine production by effector T cell subsets.
TCR signal strength controls thymic differentiation of discrete proinflammatory γδ T cell subsets.
Specimen part
View SamplesSubstantia nigra pars compacta (SNpc) is highly sensitive to normal aging and selectively degenerates in Parkinson's disease. However, ventral tegmental area (VTA), a region adjacent to SNpc, is less affected in PD. Until now, molecular mechanisms behind VTA aging have not been fully investigated using high throughput techniques.
Age-mediated transcriptomic changes in adult mouse substantia nigra.
Specimen part
View SamplesSubstantia nigra pars compacta (SNpc) is highly sensitive to normal aging and selectively degenerates in Parkinson's disease. Until now, molecular mechanisms behind SNpc aging have not been fully investigated using high throughput techniques.
Age-mediated transcriptomic changes in adult mouse substantia nigra.
Specimen part
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