c-fos基因与脊髓损伤

c-fos基因是编码核蛋白的基因，它既是一种原癌基因（protooncogene），又是即早表达基因（immediate early expression gene），机体受到多种因素刺激的时候在中枢神经系统中有c-los的表达变化。近年来研究表明，c-fos基因在正常情况下参与细胞生长、分化、信息传递、学习记忆等生理过程.而在病理情况下c-fos基因的表达和调控的变化与多种疾病的发生发展有关。本文就c-fos原癌基因在脊髓损伤中的表达变化及其功能意义和研究进展做一综述。     

c-fos基因及其蛋白表达与神经精神疾病的研究进展

c-fos基因及其蛋白表达在神经精神病学科日益受到重视,表文对c-fos基因进行了总体概述,并对c-fos基因及其所表达的蛋白结构、功能和作用进行了介绍,总结概括了c-fos基因及其蛋白表达与神经内分泌系统的关系;c-fos基因及其蛋白表达与中枢神经系统神经元细胞的关系;及其与精神科疾病的联系.     

c-fos基因与脊髓损伤

c-fos基因是编码核蛋白的基因,它既是一种原癌基因(protooncogene)[1],又是即早表达基因(immediate early expression gene),机体受到多种因素刺激的时候在中枢神经系统中有c-fos的表达变化.     

胎儿睾丸组织发育过程中精原细胞和间质细胞c-fos的表达

原癌基因c-fos是一类即刻早期基因(immediate-early gene,IEG),是细胞基因组的正常成分,作为细胞内信号传递的"第三信使",参与转录机制和核基因的表达,编码核内蛋白质,可对生殖细胞的增殖、分化、凋亡及信息传递起到调节作用。睾丸间质细胞的睾酮分泌过程也伴有某些原癌基因的表达变化。c-fos在胎儿睾丸组织发育过程中的分布和表达规律,国内未见报道。本实验旨在研究c-fos在不同阶段胎儿睾丸中定位和表达规律,为男性生殖生理学研究提供理论依据。     

c—fos基因及其蛋白表达及神经精神疾病的研究进展

c-fos基因及其蛋白表达在神经精神病学科日益受到重视,本文对c-fos基因进行了总体概述,并对c-fos基因及其所表达的蛋白结果,功能和作用进行了介绍,总结概括c-fos基因及其蛋白表达与神经内分泌系统的关系;c-fos基因臁其蛋白表达与中枢神经系统神经元细胞的关系;及其与精神科疾病的联系。     

味觉刺激与c-fos原癌基因表达

c-fos基因是一种原癌基因,属于即刻早期基因类(IEG).在口内或胃内给予各种化学刺激活,可以激活脑内相应的味觉和内脏神经元,从而引起正常大鼠及不同模型大鼠脑内相关核团中c-fos蛋白的表达.通过味觉刺激及内脏刺激与脑内核团c-fos原癌基因表达的比较研究,可为味觉信息与内脏信息在大脑中的相互作用机制提供有力的证据.     

C-FOS蛋白在癫癎定位和传播中的作用

1概述 细胞受刺激后立即表达的基因称"即早基因"(immediate early genes,IEG),包括c-fos、c-jun等.c-fos癌基因是由两类急性鼠致癌反转录病毒携带的v-fos癌基因的细胞同源序列.     

新生大鼠低氧缺血脑损伤后c-fos在脑神经元中的表达

目的：探讨c-fos基因表达在新生大鼠脑低氧缺血损伤中所起的作用。方法：采用免疫组化及逆转录扩增方法,观察新生大鼠脑低氧缺血后皮质、海马组织中c-fos基因转录、翻译水平的表达现象。结果：脑低氧缺血后早期海马和皮质部位可同时诱导出c-fos mRNA和c-fos蛋白（与sham组比较P<0.05）;皮质表达的c-fos明显低于海马（P<0.05）,非结扎侧c-fos基因一过性表达增高,但与结扎侧比较有明显差异（P<0.05）。结论：新生大鼠脑组织在低氧缺血后具备能产生特殊基因表达改变的功能,其c-fos基因的表达可能对于脑损伤后细胞的恢复与生存有重要意义。     

C-fos在多发性梗死性痴呆大鼠大脑皮层和海马的表达

目的研究即早基因c-fos与多发性梗死性痴呆(MID)的关系。方法采用微栓子注入颈内动脉的方法制备大鼠大脑多发性梗死性痴呆模型,通过免疫组织化学方法检测不同时间段大鼠脑内c-fos基因的表达。结果正常大鼠大脑皮层和海马内即有c-fos基因的表达,假手术组的表达略高于正常组(P>0.05);大鼠多发性梗死性痴呆后大脑c-fos基因过表达,在皮层和海马的表达明显高于正常对照组及假手术组(P<0.05)。随着缺血时间延长,缺血24h达高峰,持续至1个月。结论多发性梗塞性痴呆后c-fos基因呈现规律性的过表达。     

多巴胺受体在可卡因诱导的MAPK通路激活和c-fos基因表达中的作用

目的：探讨多巴胺受体对可卡因诱导的MAPK 通路及c-fos基因表达的调控作用。方法：应用多巴胺受体基因敲除 小鼠模型，采用Western blotting检测可卡因作用后2 h，MAPK家族成员ERK,JNK和p38蛋白 激酶的磷酸化活化，及早期反应基因c-fos的基因表达。结果：可卡 因急性作用下，D1多巴胺受体促进CPu区ERK激酶的激活和c-fos基因的诱导表达，D3多 巴胺受体抑制CPu区ERK激酶的激活和c-fos基因的诱导表达。而p38和JNK没有被可卡因 激活。ERK激酶的特异性抑制剂SL327可以阻断可卡因对c-fos基因的激活。结 论：D1和D3多巴胺受体对ERK激酶的激活和c-fos基因的诱导表达起相反的调 节作用，并且c-fos基因的诱导表达依赖于ERK信号通路。     

Induction of c-fos and c-jun protooncogenes expression by formaldehyde-releasing and epoxy resin-based root-canal sealers in human osteoblastic cells.

An important requirement for a root-canal sealer is biologic compatibility; most evaluations have focused on general toxicological and local tissue irritating properties. There is only scant information about mutagenicity or carcinogenicity testing for root-canal sealer. It has been shown that c-fos and c-jun are induced rapidly by a variety of chemical and physical stimuli. Numerous works have extensively investigated the induction mechanisms of c-fos and c-jun protooncogenes by these agents; however, little is known about the induction of cellular signaling events and specific gene expression after cell exposure to root-canal sealers. Therefore, we used osteoblastic cell line U2-OS to examine the effect of zinc-oxide eugenol-based (N2 and Endomethasome), epoxy resin-based (AH Plus), and calcium hydroxide-based (Sealapex) root-canal sealers on the expression of c-fos and c-jun protooncogenes to understand in more detail the molecular mechanisms of root-canal sealer-induced genotoxicity. The cytotoxicity decreased in an order of N2 > Endomethasome > AH Plus > Sealapex. In addition, N2, Endomethasome, and AH Plus rapidly induced c-jun and c-fos mRNA levels in cells. However, Sealapex did not induce c-jun and c-fos mRNA expression at detectable levels all time points. Taken together, persistent induction of c-jun and c-fos protooncogenes by formaldehyde-releasing and epoxy resin-based root-canal sealers may be distributed systemically via apex to cause some unexpected adverse effects on human beings. These data should be taken into consideration when choosing a root-canal sealer.     

Long-lasting and sequential increase of c-fos oncoprotein expression in kainic acid-induced status epilepticus

Increased but transient expression of the proto-oncogene c-fos has been recently reported in metrazol and kindling-induced seizures. Here we tested whether kainic acid-induced status epilepticus may result in a long-term increase of this oncogene. A specific pattern of immunoreactive c-fos material was observed with the development of the seizures. Intense labeling first appeared in the dentate gyrus of the hippocampus and the entorhinal cortex. Pyramidal cell layer CA3, CA4 and CA1 as well as other limbic structures were then positively stained during status epilepticus. In addition, the duration of c-fos expression was different according to the anatomical sites. In the dentate gyrus labeling did not exceed 4-5 h whereas the pyramidal cell layer CA1 exhibited increased c-fos expression for as long as 24 h. Here we propose that c-fos which has been related to growth and differentiation in previous studies, could be involved in processes inducing long-term plastic alterations in the limbic system.     

c-fos modulates brain-derived neurotrophic factor mRNA expression in mouse hippocampal CA3 and dentate gyrus neurons

Excess neuronal excitation by glutamate induces neuron cell death, which may contribute to the pathogenesis of acute brain injuries and neurodegenerative diseases. Our previous studies using a mouse with hippocampal c-fos gene deletion showed that c-fos regulates neuronal excitability and excitotoxicity. Moreover, a delayed induction of brain-derived neurotrophic factor (BDNF) protein expression in response to kainic acid (KA) treatment was found in c-fos mutant mice compared to wildtype controls, suggesting that c-fos is important in the temporal control of BDNF induction. To further investigate mechanisms of in vivo regulation of c-fos on BDNF expression, we studied the expression of BDNF mRNA and its colocalization with c-Fos protein in the hippocampal formation in the presence and absence of KA. By in situ hybridization, we observed that the c-fos mutant and wildtype mice exhibited similar basal expression of BDNF in the absence of KA. In contrast, the KA-induced BDNF mRNA levels were significantly different in wildtype and c-fos mutant mice in CA3 and dentate gyrus regions. Our findings indicate that c-fos regulates expression of BDNF in distinct neuron populations of the hippocampal formation in vivo.     

Interleukin 10 Induced C-FOS Expression in Human B Cells by Activation of Divergent Protein Kinases

IL-10 is a potent mediator of human B cell growth and plasma cell formation However, signal transduction of IL-10 in B cells is poorly understood. In this study the effect of IL-10 on the expression of the protooncogene c-fos was investigated, because Fos plays a potential role in the regulation of B cell proliferation and differentiation. B cells were purified from buffy coat preparations of healthy blood donors by positive selection using an anti CD20 monoclonal antibody and a MiniMACS separation unit. B cells were prestimulated with SAC for 48 hrs Then, cells were incubated with medium or IL-10 (100 ng/ml) for 10 to 120 min. RNA was extracted by phenol/chloroform and c-fos expression was analyzed by PCR assisted mRNA assay. A significant 2–4 fold increase of c-fos expression was observed within 30 min of stimulation with IL-10 (p < 0,01). After 2 hrs c-fos expression declined to basal levels The effect of IL-10 was dose-dependent with a maximum stimulation using 100 ng/ml of IL-10. The IL-10 effect on c-fos expression was not blocked by polymyxin B. Using the tyrosine kinase inhibitor genistein (10μM) a complete inhibition of IL-10 induced c-fos expression was observed In addition, H-7 (10μM), a specific inhibitor of serine/threonin kinases, significantly blocked IL-10 mediated c-fos expression (p < 0,05). In conclusion, these data show that IL-10 induces c-fos expression in human B-cells by activation of tyrosine and serine/threonin kinases. Since this is the first report on IL-10 induced signal transduction, these data may help to identify the intracellular mechanisms by which IL-10 stimulates human B-cells.     

c-fos protein-like immunoreactivity in cultured human glial cells

The expression of the c-fos protein(s) in cultured glial cells of the human brain and sympathetic ganglia was studied immunocytochemically using an antibody to a synthetic fragment of the c-fos protein (M-peptide). GFAP (glial fibrillary acidic protein) and S-100 antibodies were used as glial cell markers. The c-fos immunoreactivity (c-fos IR) was observed in both brain and peripheral ganglion derived cells maintained 7-22 days in culture. In general, c-fos IR was stronger in small spindle-shaped cells than in large cells. Deprivation of serum for 24 h decreased drastically c-fos IR in both types of cultures. The results demonstrate a serum-dependent expression of c-fos in the human glial cells derived from central and peripheral nervous systems.     

The expression of the immediate-early genes c-fos, egr-1 and c-jun in the accessory olfactory bulb during the formation of an olfactory memory in mice.

Female mice form a memory for the pheromones of the male with which they mate. It has been proposed that the site of the synaptic changes underlying this memory is the accessory olfactory bulb, at the first level of the accessory olfactory system. In this study we have examined the expression of the immediate-early genes c-fos, c-jun and egr-1 in the mitral and granule cells of the accessory olfactory bulb immediately after mating, during the period of memory formation. Transient increases were seen in the number of granule cell nuclei expressing c-fos and the number of granule and mitral cell nuclei expressing egr-1, during the period of memory formation. No changes were observed in the expression of c-jun during this period. The increase in the number of cells expressing c-fos and egr-1 required the association of mating and pheromonal exposure, conditions also required for memory formation. Large increases in the number of mitral and granule cell nuclei expressing c-fos and egr-1 were also observed following the infusion of the drug bicuculline into the accessory olfactory bulb in the absence of mating. This procedure has previously been shown to result in the formation of a nonspecific memory for male pheromones. These results associate the expression of c-fos and egr-1 in the accessory olfactory bulb with the conditions required for the formation of an olfactory memory for male pheromones.     

胶质瘤细胞c—fos和c—myc基因表达与血小板源生长因子B链的？…

目的 探讨胶质瘤细胞ｃ－ｆｏｓ和ｃ－ｍｙｃ基因表达和血小板源生长因子Ｂ链的纯合二聚体自分泌环活性的改变及其相互关系。方法 用原位杂交和免疫组化方法观察了６７例人胶质瘤组织。结果 ６７例中,ｃ－ｆｏｓ ｍＲＮＡ,ｃ－ｆｏｓ蛋白,ｃ－ｍｙｃ ｍＲＮＡ及ｃ－ｍｙｃ蛋白阳性率分别为;１００％,１００％,８５．１％,８３．６％。     

白细胞介素6诱导小鼠T细胞杂交瘤细胞c－fos基因表达

本文应用Ｎｏｒｔｈｅｒｎｂｌｏｔ和斑点杂交技术，观察了ｒＩＬ－６对ＩＬ－６依赖株小鼠Ｔ细胞杂交瘤细胞ＭＨ６０的ｃ－ｆｏｓ基因表达的诱导作用。结果表明：ｒＩＬ－６可明显诱导ＭＨ６０细胞ｃ－ｆｏｓ基因表达，具有剂量效应关系，且表达程度与ＩＬ－６刺激ＭＨ６０细胞增殖速率相平行，提示ＩＬ－６促肿瘤细胞分裂增殖效应是由活化ｃ－ｆｏｓ基因所介导的。