| Co-Investigator(Kenkyū-buntansha) |
ROKUTAN Kazuhito The University of Tokushima, Institute of Health Biosciences, Graduate School, Professor (10230898)
UEMURA Hirokazu The University of Tokushima, Institute of Health Biosciences, Graduate School, Lecturer (50346590)
HIYOSHI Mineyoshi The University of Tokushima, Institute of Health Biosciences, Graduate School, Assistant Professor (30363162)
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| Budget Amount *help |
¥3,710,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Research Abstract |
(1) Changes in gene expression of peripheral blood cells from women exposed to environmental cadmium
The objective of this study was to examine the effects of environmental cadmium (Cd) exposure on the gene expression profile of peripheral blood cells using an original cDNA microarray. The study population consisted of 20 female residents in a Cd-polluted area (mean age=68.7 years, Cd-exposed group) and 20 female residents in a non-Cd polluted area individually matched for age (control group).The mRNA levels of the Cd-exposed subjects were compared with those of respective controls. Median Cd concentrations in blood (3.55 μg/l) and urine (8.27 μg/g cr.)from the Cd-exposed group were 1.9-2.4 times higher than those of the control group. In cDNA microarray analysis, 137 up-regulated (>1.20-fold) and 80 down-regulated genes (<0.84-fold) were identified. Further, the authors chose 17 genes which were positively correlated with Cd concentrations in blood or urine, or which were involved in i
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mportant biological functions, and performed real-time PCR analysis. Significantly or marginally significantly increased expression was observed for CASP9, TNFRSF1B, GPX3, HYOU1, SLC3A2, SLC19A1, SLC35A4, CYP4F12, ITGAL and MT2, and significantly decreased expression was noted for BCL2A1 and COX7B. Increased expression of genes involved in protection against oxidative stress, apoptosis through the mitochondrial pathway and transporters were the characteristic features. Expression levels of SLC19A1 were positively correlated with Cd concentrations in blood and urine (r>0.5), suggesting that this was a candidate marker gene in low level exposure to environmental Cd.
(2)Introduction of proteomic approach to environmental medicine
Recent progress in life science technology and the availability of much information on genes obtained by genome analysis has enabled us to analyze the changes of proteins on a large scale. Sets of proteins are called proteomes, and proteomics is the scientific field of proteome analysis including differential, post translational modification and interaction analyses. Various proteomic techniques, particularly two-dimensional gel electrophoresis (2-DE), mass spectrometry, protein chip methods, and surface plasmon resonance (SPR), are very useful for acquiring proteomes in cells, tissues and body fluid, and for analyzing interactions between a protein and other biofactors including proteins. A proteomic approach is also useful for determining biomarkers of diseases and key proteins involved in various stages of metabolism such as differentiation, cell cycle and apoptosis. Environmental pollutants including endocrine disruptors inhibit activities of various organs in wild animals and humans. Proteomic approaches could be very useful tools for elucidating the mechanisms of damage caused by environmental pollutants. We reviewed the application of a proteomic approach to the field of environmental medicine. Less
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