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：
FUJITA Jun
金额：
$ 9.02万
依托单位：
Kyoto University
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：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390463/
关键词：
stress gene physiology gene expression hypothermia apoptosis testis 遺伝子発現

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.

在哺乳动物测试中，生殖细胞和体细胞在相对较低的温度（32-34℃）下经历活性细胞增殖和分化。为了阐明验证细胞如何适应较低的温度及其具有什么生物学意义，我们检查了基因表达的调节机制和对压力源的调节机制，在32°的体外。1。我们确定了几个人类基因的表达在32℃.2时升高。 CIRP mRNA，我们确定了以下序列，即在32℃.4.4.a balb/3t3纤维细胞中增加CIRP和其他异源mRNA的翻译，可在32℃中抗衡，并在32℃中建立了在32℃时的增殖。5。我们发现，通过抑制温度的刺激性（32℃）刺激性（32℃）诱导症状。依托泊苷，ThapseGargin，NaCl，H_2O_2，通过各种机制通过各种机制，肿瘤坏死因子（TNF）-α和抗FAS抗体。在经adrimycin处理的BALB/3T3细胞中，培养温度的下移增加了BCl-XL蛋白水平，并增加了BAX的PUMA和线粒体易位的mRNA水平，从而抑制了Caspase-9介导的凋亡。这些作用是通过抑制p53途径介导的。在用TNF-α和环己酰亚胺处理的细胞中，至少部分通过激活ERK途径的CRICP诱导了凋亡。