摘要： It is hypothesis that ATF3 is a downstream component of BMP10. The possible function of ATF3 on immune response is partially regulated by BMP10 via Smad dependent pathway. BMP10 is highly expressed in blood cells during embryonic development based on our in situ hybridization. The expression of ATF3 is enhanced by BMP10 in overexpression transgenic mice. Both BMP10 and ATF3 can response to stress stimulate, and ATF3 is well understood as a stress inducible gene which possible contributes to immune response. The Smad dependent pathway is well established for BMP10 in regulation expression of downstream targets. It would be interesting for us to determine the relationship between BMP10 and ATF3, especially to understand the mechanism of BMP10 and ATF3 effecting on heart development, as well as immune response exposed to stress stimulates. (C) 2011 Elsevier Ltd. All rights reserved.

关键词： 结直肠癌   活化转录因子   免疫组化检测   临床病理  

摘要： 目的:观察结直肠癌组织中活化转录因子2(ATF2)和活化转录因子3(ATF3)的表达并分析其表达的临床病理意义。方法:收集结直肠癌病例,明确其病理诊断并收集临床资料,应用免疫组织化学SP法检测活化转录因子2和活化转录因子3蛋白的表达。结果:ATF2在癌旁肠组织、腺瘤、腺癌组的阳性表达率分别为38%,32%,64%,差异有统计学意义,其中癌旁肠组织、腺瘤分别与腺癌有显著性差异。ATF3在癌旁肠组织、腺瘤、腺癌组的阳性表达率分别为56%,44%,52%,差异无统计学意义。ATF2表达与浸润肠壁深度,淋巴结转移有关,而与肿块大小、部位、分化程度无关。ATF3表达与肿块直径、浸润肠壁深度,而与淋巴结转移、部位、分化程度无关。结论:ATF2与结直肠癌反生和发展有关,而ATF3与结直肠癌的恶性演进有关。

关键词： 慢性阻塞性肺疾病   活化转录因子3   活化转录因子4  

摘要： 目的研究活化转录因子3(ATF3)和活化转录因子4(ATF4)在慢性阻塞性肺疾病(COPD)大鼠肺组织中的定位和表达,探讨其在COPD发病中的可能作用及意义。方法采用气管内注入脂多糖和熏香烟的方法复制大鼠COPD模型。观察COPD大鼠和正常对照组大鼠肺组织病理学改变,检测肺功能;应用原位杂交、逆转录-聚合酶链反应(RT-PCR)、免疫组化、Western blot检测大鼠肺组织中ATF3、ATF4 mRNA及蛋白的表达情况。结果 COPD组的肺功能指标(FEV0.3、FEV0.3/FVC、PEF)明显降低,光镜下肺组织病理改变符合COPD的特征性改变。免疫组化及Westernblot显示COPD组ATF3、ATF4蛋白水平较对照组升高(P<0.05);原位杂交及RT-PCR结果显示ATF3、ATF4 mRNA表达水平在COPD组显著高于对照组(P<0.05)。结论 COPD大鼠肺组织ATF3、ATF4表达明显上调,ATF3、ATF4可能参与调控COPD的氧化/抗氧化失衡。

摘要： Synapse-to-nucleus signaling triggered by synaptic NMDA receptors can lead to the buildup of a neuroprotective shield. Nuclear calcium activating the cAMP response element binding protein (CREB) plays a key role in neuroprotection acquired by synaptic activity. Here we show that in mouse hippocampal neurons, the transcription factor Atf3 (activating transcription factor 3) is a direct target of CREB. Induction of ATF3 expression by CREB in hippocampal neurons was initiated by calcium entry through synaptic NMDA receptors and required nuclear calcium transients and calcium/calmodulin-dependent protein kinase IV activity. Acting as a transcriptional repressor, ATF3 protects cultured hippocampal neurons from apoptosis and extrasynaptic NMDA receptor-induced cell death triggered by bath application of NMDA or oxygen-glucose deprivation. Expression of ATF3 in vivo using stereotaxic delivery of recombinant adeno-associated virus reduces brain damage following a cerebral ischemic insult in mice. Conversion of ATF3 to a transcriptional activator transforms ATF3 into a potent prodeath protein that kills neurons in cell culture and, when expressed in vivo in the hippocampus, ablates the neuronal cell layer. These results link nuclear calcium-CREB signaling to an ATF3-mediated neuroprotective gene repression program, indicating that activity-dependent shutoff of genes is an important process for survival. ATF3 supplementation may counteract age- and disease-related neuronal cell loss caused by a reduction in synaptic activity, malfunctioning of calcium signaling toward and within the nucleus ("nuclear calciopathy"), or increases in death signaling by extrasynaptic NMDA receptors.

关键词： Long Terminal Repeat   Cdc2 Gene   Ccne2 Gene  

摘要： Background: Adult T-cell leukemia (ATL) is an aggressive malignancy of CD4(+) T-cells caused by human T-cell leukemia virus type 1 (HTLV-1). The HTLV-1 bZIP factor (HBZ) gene, which is encoded by the minus strand of the viral genome, is expressed as an antisense transcript in all ATL cases. By using yeast two-hybrid screening, we identified activating transcription factor 3 (ATF3) as an HBZ interacting protein. ATF3 has been reported to be expressed in ATL cells, but its biological significance is not known. Results: Immunoprecipitation analysis confirmed that ATF3 interacts with HBZ. Expression of ATF3 was upregulated in ATL cell lines and fresh ATL cases. Reporter assay revealed that ATF3 could interfere with the HTLV-1 Tax's transactivation of the 5' proviral long terminal repeat (LTR), doing so by affecting the ATF/CRE site, as well as HBZ. Suppressing ATF3 expression inhibited proliferation and strongly reduced the viability of ATL cells. As mechanisms of growth-promoting activity of ATF3, comparative expression profiling of ATF3 knockdown cells identified candidate genes that are critical for the cell cycle and cell death, including cell division cycle 2 (CDC2) and cyclin E2. ATF3 also enhanced p53 transcriptional activity, but this activity was suppressed by HBZ. Conclusions: Thus, ATF3 expression has positive and negative effects on the proliferation and survival of ATL cells. HBZ impedes its negative effects, leaving ATF3 to promote proliferation of ATL cells via mechanisms including upregulation of CDC2 and cyclin E2. Both HBZ and ATF3 suppress Tax expression, which enables infected cells to escape the host immune system.

关键词： amyotrophic lateral sclerosis   astrocyte   ATF3   brain stem   motoneuron disease   neuroprotection  

摘要： Excitotoxic damage to motoneurons is thought to be an important contribution to the pathogenesis of amyotrophic lateral sclerosis (ALS), a slowly developing degeneration of motoneurons that, in most cases of sporadic occurrence, is associated with impaired glial glutamate uptake. Riluzole is the only drug licensed for symptomatic ALS treatment and is proposed to delay disease progression. As riluzole is administered only after full ALS manifestation, it is unclear if its early use might actually prevent motoneuron damage. We explored this issue by using, as a simple in vitro model, hypoglossal motoneurons (a primary target of ALS) of the neonatal rat brainstem slice preparation exposed to excitotoxic stress due to glutamate uptake block by DL-threo-beta-benzyloxyaspartate (TBOA). TBOA evoked sustained network bursting, early (1 h) enhancement of the S100B immunostaining of gray matter astrocytes, and activated the motoneuronal stress ATF-3 transcription factor;4 h later, loss (30%) of motoneuron staining ensued and pyknosis appeared. Riluzole (5 mu m;applied 15 min after TBOA) inhibited bursting, decreased the frequency of spontaneous glutamatergic events, reversed changes in S100B immunostaining and prevented late loss of motoneuron staining. These results show that excitotoxicity induced by glutamate uptake block developed slowly, and was sensed by glia and motoneurons with delayed cell death. Our data provide novel evidence for the neuroprotective action of riluzole on motoneurons and glia when applied early after an excitotoxic stimulus.