|Budget Amount *help
¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 1998 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1997 : ¥2,500,000 (Direct Cost : ¥2,500,000)
In order to elucidate the mechanisms why gene expression was regulated not only in a region-specific manner but also in a stimuli-specific manner, gene regulation of several proteins which were enriched in specific brain region was examined. Adenosine receptor subtype A2a was enriched in superior colliculs and its activation caused enhancement in visual input. Analysis of gene structure of selenoprotein RHO.which was recognized to be a survival elongation factor of neuron, displayed that its expression was regulated by metal-responsive-elements, interferon-related-elements, etc. Form-deprivation myopia caused differential regulation in nitric oxide synthase (NOS) gene in retina, namely, down regulation in iNOS and bNOS mRNAs but not F in eNOS mRNA.Aside from neurons, alteration in gene regulation was investigated, i.e., diastrophic dysplasia su1fate transporter was cloned because it was up-regulated in association with osteoblastic differentiation, while MHC-II antigens were down-regulated in lymphocytes of abused children. On the other hand, such molecular biological approach was applied to occupational health, especially, in order to elucidate neuronal toxicity of several chemicals. Anesthetic activity of alkyl acetates were associated with their hydrophobicity, namely their availability to change membrane fluidity. In case of nitriles which displayed neuronal toxicity, including behavioral abnormality, their toxicity involved in apoptosis to specific neurons. We are now investigating which apoptotic cascade is a major target to nitriles. Moreover, we are applying such approach to investigation in cancer-specific gene expression in order to clarify the mechanism of cancer progression, to estimate malignancy of each cancer, etc.