The roles and regulatory mechanisms of expression of proto-oncogenes in the nervous system

原癌基因在神经系统中表达的作用及调控机制

基本信息

批准号：
06454695
负责人：
SENBA Emiko
金额：
$ 4.03万
依托单位：
Wakayama Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454695/
关键词：
Proto-oncogenes c-fos NGFI-A (zif268)Rat Brain Stress Heart Cornea c-fos NGFI-A 視床下部室傍核

项目摘要

Immediate early genes (IEGs) are transactivated by various extracellylar stimuli. Protein products of these genes are transcription factors which link membrane deporization to long-term alterations of cellular functions. They are considered to play important roles in the neural plasticity and regeneration. In the present study, we investigated the expression patterns of these IEGs in the brain and in non-neural tissues and revealed that transcription of these IEGs is differentially regulated in various types of cells. Prior repeated immobilization stress suppresses expression of these IEGs but NGFI-A in the brain including the hypothalamic paraventricular nucleus in response to challenge stress. We also found that an elevated plasma glucocorticoid level has the same effects as repetitive stress on the regulation of these IEGs. Expression of c-fos and NGFI-A was also examined in the visual cortex in response to brief light exposure. NGFI-A was always expressed in response to light exposure and neural activation, while c-fos did not respond to light exposure in normally reared rats but responded to it only after dark rearing for one week. These findings suggest that regularly repeated stimuli suppress the responsiveness of c-fos to the stimulus. We also observed expression of IEGs in non-neuronal cells and tissues and found that immobilization stress causes transient expression of IEGs in heart muscle cells, epithelial cells of coronary arteries, or in the epithelial cells of the stomach. Regenerating corneal epithelium and skeletal muscle cells also transiently expressed these IEGs. The physiological relevance of IEGs will be investigated in our future studies using gene-manipulated aminals.

立即早期基因（IEG）被各种细胞外刺激反式激活。这些基因的蛋白质产物是将膜脱孔与细胞功能的长期改变联系起来的转录因子。它们被认为在神经可塑性和再生中发挥重要作用。在本研究中，我们研究了这些 IEG 在大脑和非神经组织中的表达模式，并揭示了这些 IEG 的转录在各种类型的细胞中受到差异性调节。先前的重复固定应激会抑制这些 IEG 的表达，但大脑中的 NGFI-A 表达（包括下丘脑室旁核）以响应挑战应激。我们还发现血浆糖皮质激素水平升高与重复应激对这些 IEG 的调节具有相同的影响。还检查了视觉皮层中 c-fos 和 NGFI-A 的表达对短暂光照的反应。 NGFI-A总是在对光照和神经激活的反应中表达，而c-fos在正常饲养的大鼠中对光照没有反应，只有在黑暗饲养一周后才产生反应。这些发现表明，定期重复的刺激会抑制 c-fos 对刺激的反应。我们还观察了 IEG 在非神经元细胞和组织中的表达，发现固定应激会导致 IEG 在心肌细胞、冠状动脉上皮细胞或胃上皮细胞中短暂表达。再生角膜上皮和骨骼肌细胞也短暂表达这些 IEG。我们将在未来的研究中使用基因操作的缩醛胺来研究 IEG 的生理相关性。