大鼠癫痫敏感性增强过程中c-jun与GFAP基因表达的关系

本文利用免疫细胞化学技术研究了海人酸(KA)致大鼠癫痫敏感性长期增强过程中,原癌基因c-jun的表达规律及其与星形胶质细胞增生、星形胶质细胞的标志物-神经胶质原纤维酸性蛋白(GFAP)基因表达的关系。一次性给予惊厥剂量(10mg/kg,i.p.)的KA后,海马CA1区出现c-jun的一过性高表达,之后呈持续表达状态直至给予KA后6个月。c-jun的表达明显地早于给予KA 2 d后方开始出现的海马内CA1区锥体细胞层神经元的死亡和C-JUN免疫反应阳性的星形胶质细胞的增生。星形胶质细胞GFAP基因的表达与其细胞内的c-jun表达的时间和部位一致。结果提示,c-jun在癫痫敏感性长期增强过程中持续表达,并可能参与介导神经元死亡和维持星形胶质细胞增生以及调控其细胞内GFAP基因的表达。     

癌基因产物c-jun和c-fos在髓母细胞瘤中的表达及临床意义

目的　了解c jun和c fos在髓母细胞瘤中的表达情况及其与预后的关系。方法　通过免疫组化方法测定c jun和c fos蛋白在 70例髓母细胞瘤和 10例正常小脑组织中的表达情况 ,并结合临床资料 ,对病人生存时间与c jun和c fos表达阳性率之间的关系进行分析。 结果　 (1)正常小脑组织标本不表达c jun和c fos;而髓母细胞瘤中多为不同程度的阳性表达 ,且以高阳性率为主 ,并发现阳性染色主要位于肿瘤细胞核 ,部分胞浆也有染色。 (2 )c jun和c fos表达呈正相关 (r =0 4 93,P <0 0 1) ;二者协同性较强。 (3)生存时间与c jun、c fos表达阳性率呈负相关 (c jun :r =- 0 4 4 7,P <0 0 1;c fos:r =- 0 5 90 ,P <0 0 1) ;c jun、c fos表达强度愈高 ,病人的生存率就愈低 ,生存时间就越短。结论　c jun和c fos在髓母细胞瘤组织中呈高表达。c jun和c fos二者在髓母细胞瘤中表达具有协同性。c jun、c fos在肿瘤中的阳性表达率与髓母细胞瘤病人的预后呈显著负相关     

孕酮对牙周膜成纤维细胞c—los、c-jun基因表达的影响

目的：研究孕酮对牙周膜成纤维细胞c—fos、c-jun基因表达的影响,探讨孕酮促进人牙周膜成纤维细胞（hPDLCs）增殖和成骨分化的可能机制。方法：原代培养hPDLCs,取第4-6代细胞用于实验。分为空白对照组,孕酮组,抑制剂组。各组细胞培养2h,采用反转录聚合酶链反应检测c—fos和c-junmRNA的表达。结果：RT—PCR的结果说明,孕酮能促进c—fos和c-junmRNA的表达,抑制剂组c—fos和c-junmRNA的表达下调。结论：孕酮能够上调hPDLCs中c—fos、c-jun的表达。提示孕酮可能通过上调c—fos、c-jun的表达促进hPDLCs的增殖和成骨分化,促进骨形成。     

B cell development is perturbed in bone marrow from c-fos/v-jun doubly transgenic mice

c-fos and c-jun gene products form a heterodimeric complex (AP-1)that regulates target gene expression by binding to a specificDNA sequence motif. In order to study a role of AP-1 (Fos/Jun)in growth and differentiation of immature B lineage cells, wehave established and mated two independent transgenic mice carryingthe mouse c-fos gene or the viral v-Jun gene fused to the H-2Kpromoter. IL-7 dependent bone marrow cell culture from doublytransgenic (H2-fos/jun) mice demonstrated severe delay of earlyB cell development. Proliferation of pre-B cells in the freshbone marrow from HZ-fos/jun mice to IL-7 stimulation was verylow. These results suggest that the deregulated production ofAP-1 perturbs IL-7 mediated proliferation and differentiationof immature B cells.     

+Gz重复暴露对大鼠脑组织c-fos、c-jun和神经生长因子基因表达的影响

为了解＋Ｇｚ重复暴露后大鼠脑组织ｃ－ｆｏｓ、ｃ－ｊｕｎ和神经生长因子基因表达的变化,探讨它们在＋ＧＫ致脑损伤中的作用和意义,用半定量反转录聚合酶链反应检测方法检测＋Ｇｚ重复暴露后大鼠脑组织ｃ－ｆｏｓ、ｃ－ｊｕｎ和ＮＧＦ ｍＲＮＡ表达水平。     

Astragalus injection inhibits c-Jun N terminal kinase mRNA expression following oxygen-glucose deprivation and reintroduction in rat hippocampal neurons

BACKGROUND： In studies concerning cell injury induced by cerebral ischemia-reperfusion, current experiments have primarily focused on altered protein levels. In addition, the apoptotic proteins Bax and Bcl-2 have been thoroughly studied with regard to initiating neuronal apoptosis. OBJECTIVE： To establish an in vitro model of oxygen-glucose deprivation and reintroduction in the rat hippocampus to simulate cerebral ischemia-reperfusion injury; to observe c-Jun N-terminal kinase 3 （JNK3） mRNA expression in hippocampal neurons following Astragalus injection; and thus to determine changes in the signaling and downstream pathways of neuronal apoptosis at the cellular and molecular level. DESIGN, TIME AND SETTING： A randomized, controlled, cellular and molecular experiment was performed at the Department of Central Laboratory, Chengde Medical College from February to June 2008. MATERIALS： Astragalus injection, the main ingredient of astragaloside, was purchased from Chengdu Di＇ao Jiuhong Pharmaceutical Manufactory, China. JNK3 mRNA probe and in situ hybridization kit were purchased from Tianjin Haoyang Biological Technology, China, and JNK3 RT-PCR primers were designed by Shanghai Bio-engineering, China. METHODS： Primary cultures of hippocampal neurons derived from Sprague Dawley rats, aged 1 2 days, were established. After 8 days, the hippocampal neurons were assigned to the following interventions： model group, Astragalus group, and vehicle control group, cells were subjected to oxygen-glucose reintroduction after oxygen-glucose deprivation for 30 minutes in sugar-free Earle＇s solution and a hypoxia device, which contained high-purity nitrogen. The normal control group was subjected to primary culture techniques and was not treated using above-mentioned interventions. In addition, the Astragalus and vehicle control groups were treated with Astragalus injection （0.5 g/L raw drug） or sterile, deionized water at 2 hours prior to oxygen-glucose deprivation, respectively. MAIN OUTCOME MEASURES： JNK3 mRNA expression was measured by in situ hybridization and RT-PCR at 0, 0.5, 2, 6, 24, 72, and 120 hours after oxygen-glucose reintroduction. RESULTS： Hippocampal neuronal morphology was normal in the normal control group. Hippocampal neurons exhibited apparent apoptosis-like pathological changes in the model, as well as the vehicle control, groups. The apoptosis-like pathological changes in the hippocampal neurons were less in the Astragalus group. Results from in situ hybridization and RT-PCR showed that JNK3 mRNA expression significantly increased in hippocampal neurons from model group, as well as the vehicle control group, compared with the normal control group （P 〈 0.05）. In addition, JNK3 mRNA expression significantly decreased in hippocampal neurons of the Astragalus group, compared with the model group and vehicle control group （P 〈 0.05）. CONCLUSION： Astragalus injection inhibited apoptosis-related JNK3 mRNA expression following oxygen-glucose deprivation and reintroduction, and accordingly played a role in inhibiting hippocampal neuronal apoptosis.     

Simvastatin induces proliferation inhibition and apoptosis in C6 glioma cells via c-jun N-terminal kinase

The lipid-lowering drugs, statins, induce apoptosis in a variety of tumor cells. Here we investigated the apoptotic effect of the lipophilic statin, simvastatin, in C6 glioma cells and the underlying effects on intracellular signal transduction. Simvastatin inhibited cell proliferation totally after 20 h of treatment as shown by the decrease in proliferating cell nuclear antigen expression in the nucleus. Subsequently, simvastatin caused apoptotic cell death by shrinkage of cytoplasm and condensation of chromatin, and DNA fragmentation. The features of apoptosis were visible only after 48 h of treatment, possibly reflecting a requirement for cell commitment to growth arrest. In immunocytochemical and immunoblotting experiments we have shown that simvastatin markedly increased the phosphorylation of ATF-2 and c-jun in the nucleus of the C6 glioma cells at early time points which was preserved even 24 h after treatment. In contrast, activities of protein kinases Erk1/2 and AKT in the cell survival pathway remained unchanged throughout the treatment. Selective inhibitor of JNK, but not p38 kinase, reduced simvastatin-induced cell death and ATF-2 and c-jun phosphorylation suggesting that JNK-dependent activation of ATF-2 and c-jun may play an important role in simvastatin-induced proliferation inhibition and apoptosis in C6 glioma cells. These observations suggest that statins may have clinical significance in the prevention of glial tumors beyond their cholesterol-lowering effect and JNK may be a rational target for sensitizing glioma cells to chemotherapeutic agents.