Project description:The excessive perchlorate utilization as an oxidizer in rocket propellants and blasting agents had led to the contamination of surface and ground waters. This chemical is known to compete with iodine for binding to the thyroid membrane receptors potentially causing hypothyroidism and fetal retardation in pregnant women. Nevertheless, to date, its biological effects are not completely understood. We have investigated the molecular mechanisms responsive to perchlorate in the nematode C. elegans to nominate a candidate gene for further peruse in the development of a C.elegans perchlorate biosensor. Perchlorate (1 mg/mL) affected the transcriptional response of Regulation of developmental process, growth, defense mechanisms and stress response, among other biological processes.
Project description:Perchlorate, which is a ubiquitous and persistent ion, competitively interferes with iodide accumulation in the thyroid, causing iodine deficiency, which may result in reduced thyroid hormone synthesis and secretion. Human studies suggest that perchlorate presents very little risk in healthy individuals; however, the precautionary principle demands that the sensitive populations of iodine deficient adults and mothers require extra consideration. In an attempt to determine if the effects on gene expression were similar, we compared the thyroidal effects of perchlorate (10 mg/kg) treatment for 14 days in drinking water with those caused by 8 weeks of Iodine-deficiency in rats. The thyroids were collected (N=3 each group) and total mRNA was analyzed using the Affymetrix Rat Genome 230 2.0 GeneChip®. Changes in gene expression were compared with appropriate control groups. We compared the 2-fold gene changes due to I-deficiency with changes due to perchlorate treatment. 189 transcripts were changed by the Iodine-deficient diet and 722 transcripts were changed by the perchlorate treatment. 34% of the transcripts changed by the I-deficient diet were also changed by perchlorate and generally in the same direction. three specific transporter genes, AQP1, NIS, & SLC22A3 were changed by both treatments, indicating that the membrane specific changes were similar. Iodine-deficiency primarily caused changes in retinol and calcium signaling pathways and perchlorate primarily caused changes related to the accumulation of extracellular matrix proteins. This study provides evidence that perchlorate, at least at this dose level, changes more genes and changes different genes compared to iodine deficiency.
Project description:Perchlorate, which is a ubiquitous and persistent ion, competitively interferes with iodide accumulation in the thyroid, causing iodine deficiency, which may result in reduced thyroid hormone synthesis and secretion. Human studies suggest that perchlorate presents very little risk in healthy individuals; however, the precautionary principle demands that the sensitive populations of iodine deficient adults and mothers require extra consideration. In an attempt to determine if the effects on gene expression were similar, we compared the thyroidal effects of perchlorate (10 mg/kg) treatment for 14 days in drinking water with those caused by 8 weeks of Iodine-deficiency in rats. The thyroids were collected (N=3 each group) and total mRNA was analyzed using the Affymetrix Rat Genome 230 2.0 GeneChip®. Changes in gene expression were compared with appropriate control groups. We compared the 2-fold gene changes due to I-deficiency with changes due to perchlorate treatment. 189 transcripts were changed by the Iodine-deficient diet and 722 transcripts were changed by the perchlorate treatment. 34% of the transcripts changed by the I-deficient diet were also changed by perchlorate and generally in the same direction. three specific transporter genes, AQP1, NIS, & SLC22A3 were changed by both treatments, indicating that the membrane specific changes were similar. Iodine-deficiency primarily caused changes in retinol and calcium signaling pathways and perchlorate primarily caused changes related to the accumulation of extracellular matrix proteins. This study provides evidence that perchlorate, at least at this dose level, changes more genes and changes different genes compared to iodine deficiency. Changes in gene expression due to I-deficiency compared to normal diet for 2 months. Changes in gene expression due to perchlorate in the drinking water compared to normal drinking water for 1 or 14 days. Feeding study in rats.
Project description:Brines, potentially formed by the deliquescence and freezing point depression of highly hygroscopic salts, such as perchlorates (ClO4-), may allow for the spatial and temporal stability of liquid water on present-day Mars. It is therefore of great interest to explore the microbial habitability of Martian brines, for which our current understanding is, however, still limited. Putative microbes growing in the perchlorate-rich Martian regolith may be harmed due to the induction of various stressors including osmotic, chaotropic, and oxidative stress. We adapted the model organism Escherichia coli to increasing sodium perchlorate concentrations and used a proteomic approach to identify the adaptive phenotype. Separately, the microbe was adapted to elevated concentrations of NaCl and glycerol, which enabled us to distinguish perchlorate-specific adaptation mechanisms from those in response to osmotic, ion and water activity stress. We found that the perchlorate-specific stress-response focused on pathways alleviating damage to nucleic acids, presumably caused by increased chaotropic and/ or oxidative stress. The significant enrichments that have been found include DNA repair, RNA methylation and de novo IMP biosynthesis. Our study provides insights into the adaptive mechanisms necessary for microorganisms to survive under perchlorate stress, with implications for understanding the habitability of Martian brines.
Project description:Arsenic and mercury are known chemical hazards. The differences in effects from organic and inorganic forms of these toxic elements is less well understood, however. The nematode Caenorhabditis elegans (C. elegans) is a suitable model to investigate the toxicity of environmental hazards. In this study, the transcriptomic profiles of C. elegans exposed to inorganic mercury chloride (HgCl2) and sodium (meta)arsenite (NaAsO2) were assessed alongside organic methylmercury chloride (meHgCl) and dimethylarsinic acid (DMA). For this purpose, adult C. elegans were exposed for 24 h to NaAsO2 (10 µg/ml), DMA (200 µg/ml), HgCl2 (2 µg/ml), and meHgCl (0.5 µg/ml), concentrations that were equitoxic in juveniles for developmental delay. Whole genome gene expression profiles were determined by using Cellegans_UnrestrictedGE_G2519F_020186 Microarray (Agilent Technologies, Santa Clara, CA). The results showed significant changes in the transcriptome of adult C. elegans exposed to NaAsO2, DMA, HgCl2, or meHgCl relative to the control group (C. elegans treated with water). A total of 927 and 1221 differentially expressed genes (DEGs) were found in C. elegans treated with 10 µg/ml NaAsO2 or 200 µg/ml DMA, respectively. Interestingly, only 161 DEGs were in common for these two chemicals. Exposure to 2 µg/ml HgCl2 or 0.5 µg/ml meHgCl altered the expression of 670 and 485 genes, respectively, and out of these genes, 154 were commonly altered by the two treatments. Analysis of DEGs revealed that organic and inorganic forms of arsenic and mercury have different effects on the transcriptome of adult C. elegans.
Project description:Potassium perchlorate (KClO4), widely used in industrial and military applications, is an emerging environmental contaminant known to disrupt thyroid function. However, its potential impact on male reproductive health remains underexplored. In this study, we investigated the testicular toxicity induced by chronic KClO4 exposure over one spermatogenic cycle of medaka (Oryzias latipes) and evaluated the ameliorative effects of vitamin C. Adult male medaka were treated with 0.01 mg/L, 10 mg/L KClO4 and 10 mg/L KClO4 plus vitamin C (3 mg/mL) for 21 days. Fertilization percentage, histological examination, and transcriptomic profiling of the testis were performed. KClO4 exposure decreased fertilization success caused disorganization of seminiferous tubules, and dysregulated spermatogenic genes in the testis. Transcriptomic analysis revealed substantial dysregulation of genes involved in cadherin and tubulin binding, chromatin remodeling, oxidative stress response, and germ cell development. Co-administration of vitamin C mitigated these effects by restoring testicular morphology, restoring fertilization rates, and partially reversing gene expression changes disrupted by potassium perchlorate exposure. The present findings suggest that vitamin C provides protective effects against perchlorate-induced testicular toxicity and highlight the need for further exploration of antioxidant-based interventions to safeguard reproductive health from perchlorate exposure.
Project description:Sodium benzoate is a widely used food antimicrobial in drinks and fruit juices. A microarray study was conducted to determine the transcriptional response of Escherichia coli O157:H7 to 0.5% (w/v) sodium benzoate. Stationary phase E. coli O157:H7 grown in 150 ml Luria-Bertani broth (LB) was exposed to 0 (control) and 0.5% sodium benzoate. Each treatment was duplicated and sampled at 0 (immediately after exposure), 5, 15, 30, and 60 min. Total RNA was extracted and analyzed with E. coli 2.0 Gene Chips.