Regulatory mechanisms of gene expression at mildly low temperature and the clinical relevance of their abnormality in the testis.
轻度低温下基因表达的调控机制及其睾丸异常的临床相关性。
基本信息
- 批准号:16390463
- 负责人:
- 金额:$ 9.02万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:2004
- 资助国家:日本
- 起止时间:2004 至 2005
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
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.
在哺乳动物睾丸中,生殖细胞和体细胞在相对低温(32-34℃)下进行活跃的细胞增殖和分化。为了阐明睾丸细胞对低温的适应及其生物学意义,我们在体外研究了32 ℃下睾丸细胞基因表达和应激反应的调控机制。在Cirp的5'端基因组序列中确定了“轻度冷反应元件”(冷诱导RNA结合蛋白)基因。3.在Cirp mRNA中,4.建立了小鼠BALB/3 T3成纤维细胞耐低温亚群,并在32℃下增殖良好。细胞毒刺激物如阿霉素、足叶乙甙、毒胡萝卜素、NaCl、H_2O_2、肿瘤坏死因子(TNF-α)和抗Fas抗体等通过多种机制抑制细胞凋亡。在阿霉素处理的BALB/3 T3细胞中,培养温度的降低增加了Bcl-xL蛋白水平,降低了Puma的mRNA水平和Bax的线粒体易位,抑制了caspase-9介导的凋亡。这些作用是通过抑制p53通路介导的。在毒胡萝卜素处理的细胞中,细胞凋亡受到p53非依赖性机制的抑制。在用TNF-α和放线菌酮处理的细胞中,通过诱导Cirp激活ERK通路,细胞凋亡至少部分受到抑制。
项目成果
期刊论文数量(31)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Apg-2 has a chaperone-like activity similar to Hsp110 and is overexpressed in hepatocellular carcinomas
- DOI:10.1016/s0014-5793(04)00034-1
- 发表时间:2004-02-27
- 期刊:
- 影响因子:3.5
- 作者:Gotoh, K;Nonoguchi, K;Fujita, J
- 通讯作者:Fujita, J
Cortical organization by the septin cytoskeleton is essential for structural and mechanical integrity of mammalian spermatozoa
- DOI:10.1016/j.devcel.2004.12.005
- 发表时间:2005-03-01
- 期刊:
- 影响因子:11.8
- 作者:Ihara, M;Kinoshita, A;Kinoshita, M
- 通讯作者:Kinoshita, M
GSTT1 and GSTM1 polymorphisms are associated with improvement in seminal findings after varicocelectomy.
GSTT1 和 GSTM1 多态性与精索静脉曲张切除术后精液检查结果的改善相关。
- DOI:
- 发表时间:2005
- 期刊:
- 影响因子:0
- 作者:Sakurai T;Sakurai T;Watanabe H;Higashitsuji H;Higashitsuji H;Okubo K
- 通讯作者:Okubo K
The oncoprotein gankyrin negatively regulates both p53 and RB by enhancing proteasomal degradation
- DOI:10.4161/cc.4.10.2107
- 发表时间:2005-10-01
- 期刊:
- 影响因子:4.3
- 作者:Higashitsuji, H;Liu, Y;Fujita, J
- 通讯作者:Fujita, J
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FUJITA Jun其他文献
FUJITA Jun的其他文献
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{{ truncateString('FUJITA Jun', 18)}}的其他基金
Elucidation of the pathophysiology of heart failure with human cardiac spheroid/organoid
用人心脏球体/类器官阐明心力衰竭的病理生理学
- 批准号:
19H03660 - 财政年份:2019
- 资助金额:
$ 9.02万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Development of the evaluation method for differentiation and maturity of human ES, iPS cell-derived cardiomyocytes with deep learning
利用深度学习开发人ES、iPS细胞来源的心肌细胞分化和成熟度评价方法
- 批准号:
19K22625 - 财政年份:2019
- 资助金额:
$ 9.02万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)
Molecular basis and clinical significance of moderately low temperature environment in the mammalian testis
哺乳动物睾丸中低温环境的分子基础及临床意义
- 批准号:
20390424 - 财政年份:2008
- 资助金额:
$ 9.02万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Molecular mchanisms of stress tolerance observed at mildly low temperature environment and the clinical relevance of their abnormality in the testis
微低温环境下睾丸应激耐受的分子机制及其异常的临床意义
- 批准号:
18390434 - 财政年份:2006
- 资助金额:
$ 9.02万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Molecular mechanism of proliteration and differentistion of male germ cells analyzed by using the cell line that undergoes "meiosis"in vitro.
利用体外“减数分裂”细胞系分析雄性生殖细胞增殖分化的分子机制。
- 批准号:
14370511 - 财政年份:2002
- 资助金额:
$ 9.02万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Functions and clinical significance of cold shock proteins in the testis
睾丸冷休克蛋白的功能及临床意义
- 批准号:
11470335 - 财政年份:1999
- 资助金额:
$ 9.02万 - 项目类别:
Grant-in-Aid for Scientific Research (B).
Temperature sensitive gene expression in male germ cells and its clinical signification
雄性生殖细胞温度敏感基因的表达及其临床意义
- 批准号:
09470345 - 财政年份:1997
- 资助金额:
$ 9.02万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Genetic Changes in Male Infertility
男性不育的基因变化
- 批准号:
04454402 - 财政年份:1992
- 资助金额:
$ 9.02万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
Molecular Oncological Analysis of Human Kidney Tumors
人肾肿瘤的分子肿瘤学分析
- 批准号:
63570747 - 财政年份:1988
- 资助金额:
$ 9.02万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
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