2005 Fiscal Year Final Research Report Summary
Regulatory mechanisms of gene expression at mildly low temperature and the clinical relevance of their abnormality in the testis.
| Project/Area Number |
16390463
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Kyoto University |
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Principal Investigator |
FUJITA Jun Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (50173430)
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| Co-Investigator(Kenkyū-buntansha) |
ITOH Katsuhiko Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (90281097)
NISHIYAMA Hiroyuki Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (20324642)
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| Project Period (FY) |
2004 – 2005
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| Keywords | stress / gene / physiology / gene expression / hypothermia / apoptosis / testis |
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| Research Abstract |
In the mammalian testes, germ cells and somatic cells undergo active cell proliferation and differentiation at relatively low temperature (32-34℃). To elucidate how testicular cells adapt to the lower temperature and what biological significance it has, we have examined the regulatory mechanisms of gene expression and response to stressors at 32℃ in vitro.
1.We identified several human genes whose expression was increased at 32℃.
2."Mild cold response element" was determined in the 5' genomic sequence of Cirp (cold-inducible RNA-binding protein) gene.
3.Within the Cirp mRNA, we identified the sequence that increased translation of Cirp and other heterologous mRNAs at 32℃.
4.A subclohe of mouse BALB/3T3 fibroblasts resistant to low temperature and able to proliferate well at 32℃ was established.
5.We found that mild hypothermia (32℃) suppressed induction of apoptosis by cytotoxic stimuli such as adriamycin, etoposide, thapsigargin, NaCl, H_2O_2, tumor necrosis factor (TNF)-α and anti-Fas antibody by various mechanisms. In adriamycin-treated BALB/3T3 cells, the down-shift in culture temperature increased the Bcl-xL protein level, and decreased the mRNA level of Puma and mitochondrial translocation of Bax, suppressing caspase-9-mediated apoptosis. These effects were mediated by suppression of the p53 pathway. In thapsigargin-treated cells, apoptosis was suppressed by p53-independent mechanisms. In cells treated with TNF-α and cycloheximide, apoptosis was suppressed, at least partly, via induction of Cirp that activated the ERK pathway.
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