检索结果-南通市图书馆

A LuxR family transcriptional regulator AniF promotes the production of anisomycin and its derivatives in Streptomyces hygrospinosus ***

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Synthetic and Systems Biotechnology 2019年第1期4卷 40-48页

作者： Jufang Shen Lingxin Kong Yan Li Xiaoqing Zheng Qing Wang Weinan Yang Zixin Deng Delin You State Key Laboratory of Microbial Metabolism Joint International Research Laboratory of Metabolic and Developmental SciencesSchool of Life Sciences&BiotechnologyShanghai Jiao Tong UniversityShanghaiChina Department of Immunology Hebei Medical UniversityShijiazhuangHebeiChina

The protein synthesis inhibitor anisomycin features a unique benzylpyrrolidine system and exhibits potent selective activity against pathogenic protozoa and *** is one of the important effective components in Agricultural Antibiotic120,which has been widely used as naturally-originated agents for treatment of crop decay in *** chemical synthesis of anisomycin has recently been reported,but the complex process with low productivity made the biosynthesis still to be a vital mainstay in *** biosynthetic gene cluster(BGC)of anisomycin in Streptomyces hygrospinosus *** has been identified in our previous work,while poor understanding of the regulatory mechanism limited the yield enhancement via regulation engineering of *** *** this study here,we characterized AniF as an indispensable LuxR family transcriptional regulator for the activation of anisomycin *** genetic manipulations of aniF and the real-time quantitative PCR(RT-qPCR)revealed that it positively regulated the transcription of the anisomycin ***,the overexpression of aniF contributed to the improvement of the production of anisomycin and its *** of the mechanism underlying the function of AniF revealed that it directly activated the transcription of the genes aniR-G involved in anisomycin ***,one AniF-binding site in the promoter region of aniR was identified by DNase I footprinting assay and an inverted repeat sequence(5′-GGGC-3′)composed of two 4-nt half sites in the protected region was *** together,our systematic study confirmed the positive regulatory role of AniF and might facilitate the future construction of engineering strains with high productivity of anisomycin and its derivatives.

关键词： anisomycin Agricultural Antibiotic120 Biosynthesis AniF LuxR regulator Streptomyces

anisomycin alleviates Experimental Autoimmune Encephalolmylitis through the reduction of pro-inflammatory cytokines and Th17 cells, and the inhibition of GFAP and Iba1?

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Anisomycin alleviates Experimental Autoimmune Encephalolmyli...

第十届全国免疫学学术大会

作者： Manman Sun Song Liu Yuhua Ji Jia Xiao Jingfang Di Shan Zeng Jing Liu Feiyue Xing Institute of Tissue Transplantation and Immunology Department of Immunobiology Jinan University

Experimental autoimmune encephalomyelitis(EAE)is a T cell-mediated autoimmune disease of the central nervous *** previous studies showed that anisomycin could obviously inhibit the proliferation and differentiation of T cells and reduce the production of inflammatory *** the current study,an EAE model was established in C57BL/6female mice by myelin oligodendrocyte glycolprotein(MOG35-55).anisomycin was used to treat the EAE-bearing mice to explore its therapeutic effect and *** mouse was subcutaneously immunized with 200μg of MOG35-55emulsified in CFA containing 5 mg/ml TB,and immediately injected intraperitoneally with pertussis ***,the mouse was administered with 400 ng of pertussis toxin once *** clinical signs in the anisomycin-treated mice were much slighter than those in the EAE-bearing *** maximum clinical sore in the EAE mice was 4.0 in the fastigium,but reduced to 2.0 by the treatment of *** maximum clinical score in the EAE mice was 3.0 in the paracmasis,but reduced to 1.5 by the treatment of anisomycin as *** with the EAE group,the demyelination of white matters and perivascular inflammatory infiltration appearing"sleeve-like"were reduced in the brain and spinal cord by the treatment of anisomycin,following the attenuation of the pro-inflammatory cytokines and chemokines as well as Th17 ***,the level of IL-17F did not significantly change dislike *** were regularities between the observed parameters and the clinical *** results indicate that anisomycin can extend the latent period in EAE-bearing mice,shorten the process of EAE progress,and reduce the pathological injury of the brain and spinal cord tissues,which involves the decreases of the pro-inflammatory cytokines and chemokines as well as Th17 cells,followed by the inhibition of GFAP and Iba1.

关键词： anisomycin GFAP Iba1 cytokine Th17 cell Experimental Autoimmune Encephalomyelitis

anisomycin suppresses Jurkat T cell growth by the cell cycle-regulating proteins

在线全文

cnki会议

学校读者我要写书评

暂无评论

Anisomycin suppresses Jurkat T cell growth by the cell cycle...

第八届全国免疫学学术大会

作者： Chunyan Yu Zhengle Tang Christian Bronner Xijian Lu Jingfang Di Shan Zeng Jing Liu Feiyue Xing Institute of Tissue Transplantation and Immunology Department of ImmunobiologyJinan University

Background:Recent studies have shown that anisomycin significantly inhibits mammalian cell proliferation, but its mechanism remains *** this study, Jurkat T cells were used to first explore a relationship between effect of anisomycin on them and alteration of cell cycle-regulating ***:Cell colony formation, CCK-8 assay, Flow cytometry, RT-PCR and Western blot were employed to evaluate correlation of ten cell cycle-regulating proteins with suppression of the cell proliferation and arrest of the cell cycle by ***:Our data showed that anisomycin inhibited the colony-formation and proliferation of Jurkat T cells in a dose-dependent manner, and arrested the cells into S and G2/M phases with the production of sub-diploid *** levels of P21, P-P27 and P53/P-P53 reached to their peaks 4 h after anisomycin treatment, presenting a positive correlation with anisomycin concentration, and P16, P-P21, P27, P57, P73/P-P73 and P- Rb changed little with the exposure time or concentrations of *** the level of Rb protein was increased at 24 h after the treatment of *** expression of an inverted CCAAT box binding protein(ICBP90) in Jurkat T cells came to decrease 12 h after the treatment of anisomycin, presenting a negative correlation with anisomycin ***, the expression of P-CDK2 was also decreased at 24 h, presenting an obviously negative correlation, whereas P-CDK1 showed no differences among the differently treated Jurkat T ***, the level of P21 and P53 mRNA was increased with the enhanced concentrations of ***:The results indicate that anisomycin may mainly activate the P53/P21 signaling to decrease the expression of ICBP90, inhibit expression of P-CDK2 to block the cells into S and G2/M phases, and finally result in proliferation inhibition of Jurkat T cells.

关键词： anisomycin P21 P53 ICBP90 CDK2 Jurkat T cell

anisomycin诱导T细胞细胞因子的差异表达及其功能

在线全文

cnki会议

学校读者我要写书评

暂无评论

anisomycin诱导T细胞细胞因子的差异表达及其功能

作者：杨云华暨南大学

学位级别：硕士

背景：作为一种抑制蛋白质合成的抗生素，anisomycin在消弱小鼠恢复创伤记忆巩固的研究由来已久。本课题组之前的体内外实验研究也证实了anisomycin能够通过影响诸如IL-2、IL-4、IFN-γ等T细胞增殖活化相关的经典细胞因子的表达进而抑制... 详细信息

背景：作为一种抑制蛋白质合成的抗生素，anisomycin在消弱小鼠恢复创伤记忆巩固的研究由来已久。本课题组之前的体内外实验研究也证实了anisomycin能够通过影响诸如IL-2、IL-4、IFN-γ等T细胞增殖活化相关的经典细胞因子的表达进而抑制T细胞的增殖、活化等生物学行为，在小鼠T细胞介导的免疫应答中起重要作用，但是anisomycin对T细胞迁移、趋化和凋亡等其它生物学行为及其相关细胞因子的表达有何影响并未见报道，本研究利用抗体芯片技术首次比较系统地分析了anisomycin诱导T细胞细胞因子的差异性表达，为探讨anisomycin抑制T细胞生物学行为的机制奠定一定的基础。目的：筛选anisomycin处理后的T细胞的细胞因子差异表达谱，探索差异表达因子MMP9和IGFBP6在anisomycin诱导T细胞凋亡中的作用。方法：免疫磁珠负选法分离小鼠淋巴结中的T细胞，用anisomycin处理T细胞，利用抗体芯片技术从144个细胞因子中筛出表达稳定差异的细胞因子;利用Trizol法提取细胞总RNA，通过RT-PCR和qPCR在mRNA水平验证差异表达因子ccl9、cxcl9、il-17e、igfbp6、ccl24和mmp9的mRNA变化。ELISA再次验证T细胞培养上清中IGFBP6和MMP9（Pro）的表达水平。选择感兴趣并差异表达稳定的MMP9和IGFBP6因子，在anisomycin处理细胞前加入JNK信号通路抑制剂SP600125，流式细胞术检测T细胞凋亡率，RT-PCR和qPCR检测mmp9、igfbp6、和jnk2mRNA水平，ELISA检测T细胞上清中MMP9、IGFBP6和相关细胞因子的含量，Western Blot检测MMP9、IGFBP6、JNK和p-JNK蛋白的变化，探讨MMP9和IGFBP6在anisomycin诱导T细胞凋亡中的作用及其与anisomycin活化的JNK信号通路有何关联。结果：anisomycin能诱导T细胞分泌的14个相关细胞因子上调，47个相关细胞因子下调。其中CCL9、CXCL9、CCL24和MMP9（Pro）细胞因子的表达明显下调，而细胞因子IL-17E和IGFBP6的表达明显上调。anisomycin处理T细胞后细胞培养上清中MMP9的水平显著降低，而IGFBP6的分泌量在anisomycin处理6h后明显上调。应用JNK信号通路抑制剂SP600125处理细胞，RT-PCR、qPCR、ELISA和Western Blot结果都显示，anisomycin处理组细胞MMP9的表达下调，而IGFBP6的表达上调，SP600125则可以不同程度逆转anisomycin的作用，提示MMP9和IGFBP6可能通过JNK信号通路的活化介导anisomycin引起的T细胞凋亡。ELISA检测显示anisomycin处理组培养上清中IL-1β和IL-6的表达都降低，IL-10和TGF-β1的表达则升高，而SP600125预处理后IL-6、IL-10和TGF-β1的表达有所逆转。结论：anisomycin可导致T细胞生成的144种细胞因子中61个因子的差异表达，其中anisomycin可以显著下调CCL9、CXCL9、CCL24和MMP9，上调IL-17E和IGFBP6的表达;anisomycin可能通过活化JNK信号通路调节T细胞MMP9和IGFBP6的表达而参与调控T细胞凋亡。

关键词： anisomycin MMP9 IGFBP6 cytokines apoptosis screen Tcells

anisomycin诱导Jurkat T细胞凋亡相关基因的差异表达及其鉴定

在线全文

同方学位论文库

学校读者我要写书评

暂无评论

anisomycin诱导Jurkat T细胞凋亡相关基因的差异表达及其鉴定

作者：霍洁暨南大学

学位级别：硕士

背景：anisomycin作为一种蛋白合成抑制剂可以诱导多种细胞发生凋亡，此前本课题组已发现anisomycin能抑制人类急性T淋巴细胞性白血病(Jurkat T)细胞增殖、阻滞细胞周期和诱导细胞凋亡，JNK信号通路的活化与anisomycin诱导Jurkat T细胞... 详细信息

背景：anisomycin作为一种蛋白合成抑制剂可以诱导多种细胞发生凋亡，此前本课题组已发现anisomycin能抑制人类急性T淋巴细胞性白血病(Jurkat T)细胞增殖、阻滞细胞周期和诱导细胞凋亡，JNK信号通路的活化与anisomycin诱导Jurkat T细胞凋亡有关，miRNA let-7c可能参与JNK信号通路的活化介导JurkatT细胞凋亡，显示其应用于T淋巴细胞性白血病临床治疗的潜在可能性。因此，探明anisomycin诱导Jurkat T细胞凋亡的机制具有重要的科学意义。目前已发现哺乳动物细胞存在诸多与细胞凋亡相关的基因，在anisomycin诱导Jurkat T细胞凋亡过程中究竟有哪些细胞凋亡相关基因参与？它们是否与JNK/miRNAlet-7c关联？本研究利用qPCR基因芯片技术首次比较系统地分析了anisomycin诱导Jurkat T细胞凋亡相关基因的的差异性表达谱，以期进一步阐明anisomycin诱导Jurkat T细胞凋亡的机制，为其临床应用奠定一定基础。目的：通过qPCR基因芯片技术筛选anisomycin诱导Jurkat T细胞凋亡相关基因的差异表达谱，确证差异表达基因E2F2是否与anisomycin诱导Jurkat T细胞凋亡有关，E2F2分子与介导anisomycin诱导Jurkat T细胞凋亡的miRNA let-7c之间是否存在关联。方法：镜下观察不同浓度anisomycin处理组Jurkat T细胞形成集落的大小和数量;荧光显微镜下观察不同浓度anisomycin处理后Jurkat T细胞核染色质形态的变化;流式细胞术分析不同浓度anisomycin作用下Jurkat T细胞的凋亡率;qPCR基因芯片从88种细胞凋亡相关基因中筛选anisomycin作用后差异表达显著的13个基因;RT-PCR和qPCR在mRNA水平验证筛选出显著差异表达的基因，从中选出感兴趣的E2F2以确定其作用。转染miRNA let-7c模拟物和miRNAlet-7c抑制剂至Jurkat T细胞中，流式细胞术检测细胞凋亡率，qPCR和WesternBlot分别在基因和蛋白水平检测miRNA let-7c和E2F2的含量变化以证实miRNAlet-7c和E2F2与Jurkat T细胞凋亡是否有关;转染E2F2siRNA至Jurkat T细胞中，流式细胞术检测细胞凋亡率，qPCR和Western Blot分别在基因水平和蛋白水平检测let-7c和E2F2的含量变化以进一步确证E2F2与miRNA let-7c介导anisomycin诱导Jurkat T细胞凋亡是否关联。*结果：随着anisomycin浓度的升高，Jurkat T细胞集落变小和数量减少;JurkatT细胞核皱缩，凋亡小体形成，凋亡细胞百分比与anisomycin的浓度成依赖性递增。qPCR基因芯片分析显示，anisomycin处理Jurkat T细胞1h后，AIFM2、CAS5、CD226、CD27、CIDEA、DAPK2、EGFR、ERBB3、FADD、FASLG、IFNA2、IFNB1、IGF1、IGF1R、IKBKG、IL10、IL1A、IL1B、IL6R、IL7、MAP3K1、MAP3K10、 MAP3K14、 NTRK1、 PDCD1、 PPP3CC、 STAT1、 STAT5B和TNFRSF10A共29个基因表达上调，AKT2、AKT3、CAS4、CD24、E2F2、EndoG、IKBKB、IL4、MAP3K5、PIK3R2、TNF和TNFRSF10B共12个基因表达下调，其中，CD226、FADD和IL1B上调高达20～45倍，AKT2、CD24、E2F2、EndoG、IL4和PIK3R2基因下调10～20倍。anisomycin处理Jurkat T细胞6h后，APAF1、API5、CAS7、CAS9、CD226、CD27、E2F2、ERBB3、IFNB1、IGF1R、IL2、RIPK1、STAT1、TNFRSF10A和XIAP15个基因表达上调，DAPK3、FASLG、IKBKG、IL6R和IRAK15个基因表达下调，其中，CAS7、CAS9、CD226、IL2和TNFRSF10A5个基因上调达10～20倍，而FASLG和IL6R下调均达15倍左右。筛选出差异倍数10倍以上的13个基因，即CD226、CD24、E2F2、FASLG、TNFRSF10A、CAS7、CAS9、PIK3R2、IKBKB、AKT2、AKT3、FADD和EndoG，qPCR显示E2F2、PIK3R2、IKBKB、CD24、CAS9、CD226和TNFRSF10A7基因的qPCR结果与芯片的结果一致。miRNA let-7c可以促进Ju

关键词： anisomycin 基因芯片筛选 E2F2 miRNA let-7c 凋亡 Jurkat T

anisomycin通过JNK/miRNAlet-7c/AP-1/STAT1/STAT3信号诱导Jurkat T细胞凋亡

在线全文

同方学位论文库

学校读者我要写书评

暂无评论

anisomycin通过JNK/miRNAlet-7c/AP-1/STAT1/STAT3信号诱导Jurkat...

作者：周志伟暨南大学

学位级别：硕士

背景:micro RNAs(mi RNAs)是一类在转录后水平负调基因表达的非编码小RNA分子,已有研究表明mi RNAs与凋亡关系密切。anisomycin由链霉菌(Streptomyces griseolus)分泌,能与60S核糖体中亚单位28S r RNA结合并阻断肽键形成,从而阻止肽链... 详细信息

背景:micro RNAs(mi RNAs)是一类在转录后水平负调基因表达的非编码小RNA分子,已有研究表明mi RNAs与凋亡关系密切。anisomycin由链霉菌(Streptomyces griseolus)分泌,能与60S核糖体中亚单位28S r RNA结合并阻断肽键形成,从而阻止肽链延长和导致多核糖体降解。此前本课题组已筛选并鉴定出在anisomycin诱导人类急性T淋巴细胞性白血病(Jurkat T)细胞凋亡中显著差异表达的mi RNA let-7c。然而,let-7c被anisomycin刺激表达上调后,它是如何介导Jurkat T细胞凋亡的以及与JNK通路是否存在关联尚不清楚。目的:深入阐明mi RNA let-7c(let-7c)在anisomycin诱导Jurkat T细胞凋亡中的作用与可能机制,以期为anisomycin临床应用于治疗白血病提供理论基础和实验依据。方法:建立anisomycin体外诱导Jurkat T细胞凋亡的模型。anisomycin处理细胞前加入JNK信号通路特异性阻断剂SP600125,q PCR检测let-7c的变化,以探明JNK信号与let-7c之间是否存在关联;通过分别转染let-7c-mimic、let-7c-inhibitor和let-7c过表达载体,结合流式细胞术分析let-7c在anisomycin诱导Jurkat T细胞凋亡中的作用,用Western Blot观察let-7c对凋亡相关转录因子AP-1、P-AP-1、STAT1、P-STAT1、STAT3、P-STAT3和凋亡相关蛋白Bim、P-Bim、Bcl-x L、P-Bcl-x L表达的影响,以确定anisomycin是否通过let-7c影响这些凋亡相关因子;进一步采用RT-PCR、q PCR和Western Blot确证let-7c与Bim和Bcl-x L的关联;再利用si RNA技术沉默Jurkat T细胞中的bim基因,结合流式细胞术、q PCR和Western Blot确证Bim是否在let-7c介导anisomycin诱导Jurkat T细胞凋亡中发挥作用;最后,通过Western Blot和原位免疫荧光染色观察Bim能否影响Jurkat T细胞中活化的Bax和Bak的表达与分布,以弄清Bim激活的下游分子及其作用。结果:anisomycin显著上调mi RNA let-7c的表达,但是这种作用可被JNK通路阻断剂SP600125部分逆转。anisomycin明显增加Jurkat T细胞早期凋亡和晚期凋亡细胞比例,转染let-7c-mimic或let-7c过表达载体均可发挥类似的促凋亡作用,而转染let-7c-inhibitor可部分逆转anisomycin诱导的凋亡。let-7c-mimic、let-7c过表达或anisomycin都能上调P-AP-1和P-STAT1蛋白水平,而anisomycin的上调作用可被let-7c-inhibitor部分逆转。相反,P-STAT3表达被let-7c-mimic、let-7c过表达载体或anisomycin抑制,而let-7c-inhibitor却能逆转anisomycin的抑制作用。同时,无论anisomycin还是let-7c-mimic和let-7c-inhibitor均不改变非磷酸化的AP-1、STAT1和STAT3。let-7c-mimic能够上调Bim m RNA、蛋白和磷酸化水平,而下调Bcl-x L m RNA和蛋白水平,但不影响P-Bcl-x L的表达。低敲bim基因能明显减少anisomycin诱导的Jurkat T细胞凋亡,抑制anisomycin对Bak和Bax蛋白的结构性活化,呈现active Bak和active Bax蛋白水平的降低,而非活性的Bax无变化。结论:anisomycin可能通过JNK/let-7c/AP-1/STAT1/STAT3信号通路打破促凋亡性BH3-Only蛋白Bim与抗凋亡性Bcl-2家族成员Bcl-x L之间的平衡,从而激活Bak/Bax,最终导致Jurkat T细胞的凋亡。

关键词： ]:miRNA let-7c anisomycin 凋亡 Jurkat T

anisomycin体内抗CT26小鼠结肠癌效果及其机制初探

在线全文

同方学位论文库

学校读者我要写书评

暂无评论

anisomycin体内抗CT26小鼠结肠癌效果及其机制初探

作者：傅海锋暨南大学

学位级别：硕士

背景：有文献报道anisomycin在体外能诱导多种细胞凋亡，本研究组之前首次尝试将anisomycin应用于体内治疗艾氏腹水瘤和黑色素瘤，发现它能抑制艾氏腹水瘤的生长，明显延长荷瘤小鼠存活期。而有关anisomycin体内给药对其它不同组织学类... 详细信息

背景：有文献报道anisomycin在体外能诱导多种细胞凋亡，本研究组之前首次尝试将anisomycin应用于体内治疗艾氏腹水瘤和黑色素瘤，发现它能抑制艾氏腹水瘤的生长，明显延长荷瘤小鼠存活期。而有关anisomycin体内给药对其它不同组织学类型肿瘤是否有效迄今尚未见报道。显然，进一步尝试和探索anisomycin体内治疗消化系统肿瘤的可能性具有重要的理论意义，可望为其临床应用提供实验依据。目的：探索anisomycin体内治疗小鼠结肠癌CT26的可能性及其初步抗肿瘤机制。方法：在体外以CT26细胞为模型，用MTT法检测不同浓度anisomycin处理不同时间对细胞增殖的影响;应用流式细胞术检测anisomycin处理后CT26细胞的生长周期和细胞凋亡;Western blot分析不同药物浓度和不同处理时间对CT26细胞凋亡相关蛋白表达的影响。在体内建立荷CT26实体瘤BALB/c小鼠模型，瘤内注射5mg/kg anisomycin,以同剂量的adriamycin治疗作为阳性对照。观察小鼠肿瘤生长情况、存活时间和免疫器官的变化;HE染色观察肿瘤组织病理改变和淋巴细胞浸润;TUNEL法与流式细胞术检测肿瘤组织内细胞凋亡变化;Western blot分析肿瘤组织内凋亡相关蛋白的表达水平;免疫组织化学法检测肿瘤标记物癌胚抗原（carcino-embryonic antigen, CEA）在肿瘤组织中的表达情况;ELISA检测荷瘤小鼠血清中相关细胞因子水平。结果：anisomycin在体外能够显著抑制CT26肿瘤细胞的增殖，处理48h和72h后抑制率最为明显;anisomycin组的细胞增殖抑制率高于adriamycin组。随着anisomycin浓度升高，sub-G0/G1期细胞增加，而G0/G1细胞减少，晚期细胞凋亡比例增加，caspase-3、cleaved caspase-3、cleaved caspase-8和cleaved caspase-9等凋亡蛋白的水平也随之升高。与对照组比较，anisomycin治疗组小鼠的肿瘤体积明显缩小，瘤重减轻，存活时间显著延长，而adriamycin治疗组的肿瘤亦明显缩小，但小鼠存活时间低于anisomycin治疗组;anisomycin治疗组小鼠的胸腺系数增高，脾系数减低，肿瘤组织的细胞凋亡比例显著高于本课题受国家自然科学基金项目（No.81172824）资助.对照组与adriamycin治疗组，肿瘤组织细胞中caspase-3、cleaved caspase-3、cleaved caspase-8和cleaved caspase-9明显上调，并与原位肿瘤组织细胞的凋亡变化一致;anisomycin治疗组和adriamycin治疗组肿瘤组织中CEA在组织中的表达量似低于对照组。anisomycin治疗组小鼠血清中INF-γ、TNF-α和TGF-β的水平亦高于对照组。结论：结果表明，anisomycin在体内能够显著抑制结肠癌CT26的生长，增加荷瘤小鼠的存活率，其抗肿瘤作用可能与anisomycin抑制CT26细胞增殖和周期、激活caspase途径诱导肿瘤细胞凋亡密切相关。

关键词： anisomycin CT26 治疗细胞凋亡小鼠

E2F2 negatively regulates miRNA let-7c to balance the anisomycin-triggered apoptosis of Jurkat T cells

在线全文

同方学位论文库

学校读者我要写书评

暂无评论

E2F2 negatively regulates miRNA let-7c to balance the anisom...

第十届全国免疫学学术大会

作者： Jie Huo Jia Xiao Yuhua Ji Yu Xia Jingfang Di Shan Zeng Jing Liu Feiyue Xing Institute of Tissue Transplantation and Immunology Department of Immunobiology Jinan University

anisomycin is considered as a protein synthesis *** research group has previously found that anisomycin can inhibit cell proliferation,arrest cell cycle and especially induce apoptosis of tumor *** genes related to cell apoptosis are involved in the mechanistic process of anisomycin?Here we found that the size and number of colony formation of Jurkat T cells were obviously reduced with the increasing concentration of anisomycin,followed by the cell nuclear shrinkage,the formation of apoptotic bodies,and the augmented percentage of apoptotic *** the treatment of anisomycin,the expressions of 15 genes,including apaf1,api5,cas7,cas9,cd226,cd27,e2f2,erbb3,ifnb1,igf1r,il2,ripk1,stat1,tnfrsf10a and xiap,were up-regulated,but the expressions of 5 genes,i.e.,dapk3,faslg,ikbkg,il6r and irak1,were down-regulated in Jurkat T cells through the gene array *** them,cas7,cas9,cd226,il2and tnfrsf10a were increased to 100 fold,but both faslg and il6r were decreased by approximitely about 15 *** alterations of E2F2,CD24,IKBKB,AKT2,CAS9,CD226,and TNFRSF10A were further confirmed to be consistent with the data obtained using the gene ***,E2F2 was focused on the apoptotic process of the *** RNA let-7c mimics facilitated the enhancement of E2F2 in the anisomycin-triggered cell apoptosis,which could be reversed by using micro RNA let-7c *** knockdown of e2f2 gene resulted in the inhibition of the cell apoptosis,followed by the increase of micro RNA let-7c to some *** opposite effect was also observed in the same ***,in the process of the anisomycin-induced apoptosis of Jurkat T cells,there exists a correlation between E2F2 and mi RNA let-7c,appearing as a negative feedback circuit.

关键词： anisomycin gene array E2F2 micro RNA let-7c apoptosis Jurkat T

Novel antineoplastic mechanism of anisomycin targeting hepatocellular carcinoma

在线全文

cnki会议

学校读者我要写书评

暂无评论

Novel antineoplastic mechanism of anisomycin targeting hepat...

第十二届全国免疫学学术大会

作者： Lv Yi Xiong Yongjia Liu Yingxia Ouyang Songying Li Yun Qiu Shiqiao Tipoe George L Xiao Jia Xing Feiyue Department of Immunobiology Institute of Tissue Transplantation and ImmunologyJinan University State Key Discipline of Infectious Diseases Shenzhen Third People's Hospital National Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of Sciences School of Biomedical Sciences The University of Hong Kong

Hepatocellular carcinoma(HCC) is the third leading cause of cancer-related mortality *** drugs have,to date,been developed with sufficient therapeutic ***,we explored for the first time the potent anti-HCC effects of anisomycin and its possible mechanistic *** vitro and in vivo various hepatocellular carcinoma models were established to validate therapeutic effects of anisomycin using multi-biobehaviours-evaluating *** and TSA were utilized to find which receptors on cellular membrane might interact with anisomycin to transfer signaling across the ***,intracytoplasm and intranucleus signaling molecules were firstly predicted through the STRING ***,their interactions and functions were tested in the foregoing models and clinical cases by multi-strategies and *** results showed that anisomycin selectively suppressed hepatocyte carcinogenesis and hepatoma growth,and induced *** interacted with frizzled(FZD) 3 and specially FZD6 receptors on the cell membrane before triggering signal *** proliferator-activated receptor delta(PPAR8) and Nod-like receptor protein 3(NLRP3) showed the differential expression patterns in clinical HCC cases and exerted the opposing effects in the down-stream signaling of a wingless/int1(Wnt)/β-catenin pathway,which involved heat shock protein 90(HSP90) as a direct ***,a moderate over-expression of the endogenous NLRP3 protein in HCC cells elicited the potent suppressive effects on the *** study reveals for the first time the novel activity and mechanism of anisomycin against HCC through directly targeting the FZD6/PPARδ/HSP90/NLRP3 signaling pathway,indicating its potentially clinical application to treatment of human HCC.

关键词： anisomycin FZD6 PPARδ HSP90 NLRP3 Hepatocellular Carcinoma