Knowledge Building Insights on Biomarkers of Arsenic Toxicity to Keratinocytes and Melanocytes
| Autor: | O. R. Awofolu, Andreas N. Mbah, Kafui Edusei, Matilda O. Johnson, Udensi K. Udensi, Michael A Bauer, Matthew N. Anyanwu, Raphael D. Isokpehi, Roger A. Hall |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
melanocyte
environmental response genes keratinocyte Melanocyte Biology Bioinformatics 03 medical and health sciences 0302 clinical medicine TFRC medicine Transcription factor E2F4 Gene 030304 developmental biology Original Research Pharmacology 0303 health sciences lcsh:R5-920 Arsenic toxicity skin cancer integumentary system iron uptake Biochemistry (medical) arsenic functional annotation 3. Good health Cell biology vicinal cysteines Isokpehi et al medicine.anatomical_structure 030220 oncology & carcinogenesis Skin hyperpigmentation toxicogenomics Molecular Medicine hyperpigmentation disulfide bond Keratinocyte Toxicogenomics lcsh:Medicine (General) RAC1 SNPs |
| Zdroj: | Biomarker Insights, Vol 2012, Iss 7, Pp 127-141 (2012) Biomarker Insights, Vol 7 (2012) Biomarker Insights |
| ISSN: | 1177-2719 |
| Popis: | Exposure to inorganic arsenic induces skin cancer and abnormal pigmentation in susceptible humans. High-throughput gene transcription assays such as DNA microarrays allow for the identification of biological pathways affected by arsenic that lead to initiation and progression of skin cancer and abnormal pigmentation. The overall purpose of the reported research was to determine knowledge building insights on biomarker genes for arsenic toxicity to human epidermal cells by integrating a collection of gene lists annotated with biological information. The information sets included toxicogenomics gene-chemical interaction; enzymes encoded in the human genome; enriched biological information associated with genes; environmentally relevant gene sequence variation; and effects of non-synonymous single nucleotide polymorphisms (SNPs) on protein function. Molecular network construction for arsenic upregulated genes TNFSF18 (tumor necrosis factor [ligand] superfamily member 18) and IL1R2 (interleukin 1 Receptor, type 2) revealed subnetwork interconnections to E2F4, an oncogenic transcription factor, predominantly expressed at the onset of keratinocyte differentiation. Visual analytics integration of gene information sources helped identify RAC1, a GTP binding protein, and TFRC, an iron uptake protein as prioritized arsenic-perturbed protein targets for biological processes leading to skin hyperpigmentation. RAC1 regulates the formation of dendrites that transfer melanin from melanocytes to neighboring keratinocytes. Increased melanocyte den-dricity is correlated with hyperpigmentation. TFRC is a key determinant of the amount and location of iron in the epidermis. Aberrant TFRC expression could impair cutaneous iron metabolism leading to abnormal pigmentation seen in some humans exposed to arsenicals. The reported findings contribute to insights on how arsenic could impair the function of genes and biological pathways in epidermal cells. Finally, we developed visual analytics resources to facilitate further exploration of the information and knowledge building insights on arsenic toxicity to human epidermal keratinocytes and melanocytes. |
| Databáze: | OpenAIRE |
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