Project description:In the present study, we employed the RNA sequencing platform to examine the molecular response of zebrafish liver to arsenic exposure and carry out detailed transcriptomic analyses for further understanding of molecular toxicity. We found that several important biological processes were perturbed by arsenic exposure, including oxidation reduction, translation, iron ion transport, cell redox and homeostasis, as well as related pathways in metabolism and diseases. Furthermore, as there are currently no biomarker genes available for predicting arsenic exposure, we took the advantage of RNA sequencing platform to identify most suitable biomarker genes from top responsive genes to arsenic exposure. We first validated these top responsive genes by RT-qPCR in zebrafish and then in Japanese medaka (Oryzias latipes) at individual fish level for more robustly responsive genes across different fish species. Transcriptome profiling of arsenic-treated sample and control sample were generated by deep sequencing using 3' RNA-SAGE on the SOLiD system.
Project description:Talemi2014 - Arsenic toxicity and
detoxification mechanisms in yeast
The model implements arsenite (AsIII)
transport regulation, its distribution within main cellular AsIII
pools and detoxification. The intracellular As pools considered are
free AsIII (AsIIIin), protein-bound AsIII (AsIIIprot), glutathione
conjugated AsIII (AsGS3) and vacuolar sequestered AsIII (vAsGS3).
This model is described in the article:
Mathematical modelling of
arsenic transport, distribution and detoxification processes in
yeast.
Talemi SR, Jacobson T, Garla V,
Navarrete C, Wagner A, Tamás MJ, Schaber J.
Mol. Microbiol. 2014 Jun; 92(6):
1343-1356
Abstract:
Arsenic has a dual role as causative and curative agent of
human disease. Therefore, there is considerable interest in
elucidating arsenic toxicity and detoxification mechanisms. By
an ensemble modelling approach, we identified a best
parsimonious mathematical model which recapitulates and
predicts intracellular arsenic dynamics for different
conditions and mutants, thereby providing novel insights into
arsenic toxicity and detoxification mechanisms in yeast, which
could partly be confirmed experimentally by dedicated
experiments. Specifically, our analyses suggest that: (i)
arsenic is mainly protein-bound during short-term (acute)
exposure, whereas glutathione-conjugated arsenic dominates
during long-term (chronic) exposure, (ii) arsenic is not stably
retained, but can leave the vacuole via an export mechanism,
and (iii) Fps1 is controlled by Hog1-dependent and
Hog1-independent mechanisms during arsenite stress. Our results
challenge glutathione depletion as a key mechanism for arsenic
toxicity and instead suggest that (iv) increased glutathione
biosynthesis protects the proteome against the damaging effects
of arsenic and that (v) widespread protein inactivation
contributes to the toxicity of this metalloid. Our work in
yeast may prove useful to elucidate similar mechanisms in
higher eukaryotes and have implications for the use of arsenic
in medical therapy.
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Project description:Ground water Arsenic toxicity is the global problem and millions of people are exposed to elevated levels through drinking water than WHO permiscible limit of 10µg/L. The exposure is associated with various cancerous and non-cancerous diseases. It may alter the gene expression profile of invidual and suppress the activity of various genes giving rise to different diseases. Pakistan, a developing country in South Asian region, also have different areas reported to have elevated Ground water As. levels since 2005. The Present Study aimed to investigate Transcriptome profile of the exposed subjects in two districts of Punjab Province Pakistan. i.e Lahore and Kasur. The population was stratified into three exposure groups comprising Low, Medium and High exposure based on their urinary arsenic levels. We used Agilent Microarrays platform for Transcriptomics analysis and Linear mixed model was used to find differential gene expression associated with Arsenic exposure
Project description:Chronic exposure to arsenic is associated with dermatological and non-dermatological disorders. Consumption of arsenic contaminated drinking water results in accumulation of arsenic in liver, spleen, kidneys, lungs and gastrointestinal tract. Although, arsenic is cleared from these sites, a substantial amount of residual arsenic is left in keratin-rich tissues such as skin. Epidemiological studies on arsenic suggest the association of skin cancer upon arsenic exposure, however, the exact mechanism of arsenic induced carcinogenesis is not completely understood. We have developed a cell line-based model to understand the molecular mechanisms involved in arsenic mediated toxicity and carcinogenicity. Human skin keratinocyte cell line, HaCaT was exposed to 100nM sodium arsenite for six months. We observed an increase in the basal ROS levels in arsenic exposed cells along with the increase in anti-apoptotic proteins. SILAC-based quantitative proteomics approach resulted in the identification and quantitation of 2,181 proteins of which 39 proteins were found to be overexpressed (≥2-fold) and 56 downregulated (≤2-fold) upon chronic arsenic exposure. Our study provides comprehensive insights into the molecular basis of chronic arsenic exposure on skin.
Project description:Arbuscular mycorrhizal symbiosis is a predominant relationship between plant and arbuscular mycorrhizal fungi. To idendify arbuscular mycorrhiza responsive miRNAs, small RNA libraries were constructed in tomato roots colonized with Rhizophagus irregularis and without Rhizophagus irregularis. We identify miRNAs in tomato roots and provide a new profile of tomato miRNAs. And we found that some miRNAs were responsive to arbuscular mycorrhiza by comparing miRNAs in treatment with that in control. Examination of arbuscular mycorrhiza responsive miRNAs in tomato through high-throughput small RNA sequencing of roots with Rhizophagus irregularis and that without Rhizophagus irregularis