2005 Fiscal Year Final Research Report Summary
Functional analysis of differentially expressed genes involved in testicular dysfunctions induced by endocrine disrupting chemicals
| Project/Area Number |
16590091
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental pharmacy
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| Research Institution | UNIVERSITY OF TOYAMA (2005)
Toyama Medical and Pharmaceutical University (2004) |
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Principal Investigator |
TABUCHI Yoshiaki University of Toyama, Life science research Center, Associate Professor, 生命科学先端研究センター, 助教授 (20322109)
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| Project Period (FY) |
2004 – 2005
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| Keywords | endocrine disrupting chemical / bisphenol A / simian virus 40 large-T antigen / Sertoli cell / epididymis caput cell / gene expression / microarray |
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| Research Abstract |
A conditionally immortalized epididymis caput cell line, MEPC5,was established by infecting primary cultured mouse epididymis caput cells with a temperature-sensitive simian virus 40 large T (tsSV40LT)-antigen. At a permissive temperature 33℃, the large T-antigen was expressed and the cells grew continuously. However, the down regulation of T-antigen at a nonpermissive temperature of 39℃ and the upregulation of cell density at 33℃ were associated with growth arrest and the increased protein expression of p21^<waf1>. The cells expressed epididymal caput-expressed genes such as ME1,sulfated glycoprotein-2 (SGP-2) and androgen receptor. Interestingly, the expression levels of ME1 and SGP-2 were significantly elevated under the cell growth-restricted conditions.
Testicular Sertoli TTE3 cells, established from transgenic mice bearing tsSV40LT-antigen, proliferated continuously at 33℃ whereas inactivation of the large T-antigen by 39℃ led to differentiation. To clarify the detailed mechanisms of differentiation, we investigated the time course of changes in gene expression using cDNA microarrays. Of the 865 genes analyzed, 14 genes showed increased levels of expression. Real-time quantitative PCR revealed that the mRNA levels of p21^<waf1>, milk fat globule membrane protein E8,heat-responsive protein 12,and selenoprotein P were markedly elevated.
Taken together, mouse epididymis caput epithelial MEPC5 and mouse testicular Sertoli TTE3 cells should prove an excellent model for studies of gene expression and endocrine disrupting chemicals in the male reproductive systems. In previous our experiments, 31 genes such as fra-2,c-myc, and ornithine decarboxylase (ODC) were identified as up-regulated genes responsive to bisphenol A in Sertoli TTE3 cells. At present, roles of fra-2,c-myc, and ODC in male reproductive dysfunctions caused by endocrine disrupting chemicals have been investigated using these established cell lines.
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Research Products
(10 results)
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[Journal Article] Therapeutic potential of follistatin for colonic inflammation in mice2005
Author(s)
Dohi, T., Ejima, C., Kato, R., Kawamura, Y.I., Kawashima, R., Mizutani, N., Tabuchi, Y., Kojima, I.
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Journal Title
Gastroenterology 128
Pages: 411-423
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Functional characterization of a conditionally immortalized mouse epididymis caput epithelial cell line MEPC5 using temperature-sensitive simian virus 40 large T-antigen2005
Author(s)
Tabuchi, Y., Toyama, Y., Toshimori, K., Komiyama, M., Mori, C., Kondo, T.
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Journal Title
Biochem Biophys.Res.Commun. 329
Pages: 812-823
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Apoptosis induced by the sonomechanical effects of low intensity pulsed ultrasound in a human leukemia cell line2005
Author(s)
Feril, L.B., Jr., Kondo, T., Cui, Z.-G., Tabuchi, Y., Zhao, Q.-L., Ando, H., Misaki, T., Yoshikawa, H., Umemura, S.
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Journal Title
Cancer Lett. 221
Pages: 145-152
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Analysis of gene expression in apoptosis of human lymphoma U937 cells induced by hyperthermia and the effects of α-phenyl N-tert-butylnitrone (PBN) and its derivatives2005
Author(s)
Hirano, H., Tabuchi, Y., Kondo, T., Zhao, Q.-L., Ogawa, R., Cui, Z.-G., Feril, L.B., Jr., Kanayama, S.
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Journal Title
Apoptosis 10
Pages: 331-340
Description
「研究成果報告書概要(欧文)」より
