维甲酸与精子发生

维生素A的活性代谢物维甲酸在哺乳动物精子发生过程中发挥着重要的调节作用,但其具体调节机制并不十分清楚。该文拟对睾丸内维甲酸的运输、代谢、信号系统以及维甲酸调控精子发生的研究进展进行简单总结。     

全反式维甲酸对急性早幼粒细胞白血病患者血清学的影响

目的：探讨全反式维甲酸（All trans retinoic acid,ATRA）作为辅助剂在急性早幼粒细胞白血病（Acute promyelocytic leukemia, APL）治疗中,对患者血清促红细胞生成素（Erythropoietin,EPO）、血清铁蛋白、叶酸和维生素B12水平的影响。方法：回顾性分析 我院2011 年6 月-2015 年6 月接诊的50 例急性早幼粒细胞白血病患者的临床资料。根据患者的治疗方法不同将患者分为两组, A 组（亚砷酸钠治疗组）和B 组（亚砷酸钠联合ATRA）。对比两组患者治疗后血清铁蛋白、EPO、叶酸和维生素B12 恢复情况。结 果：两组患者入院时所有血清EPO、铁蛋白等比较,差异无统计学意义（P>0.05）;治疗后两组患者血清各指标均有所改善（P<0. 05）;治疗后B 组患者中EPO、血清B12、血清铁蛋白和叶酸恢复正常水平者明显多于A 组,差异具有统计学意义（P<0.05）。结论： 全反式维甲酸辅助治疗急性早幼粒细胞白血病患者能够更好的改善患者血清EPO、铁蛋白、叶酸和维生素B12 的异常,对于疾病 的治疗有一定的效果。     

All-Trans Retinoic Acid Activity in Acute Myeloid Leukemia: Role of Cytochrome P450 Enzyme Expression by the Microenvironment

Differentiation therapy with all-trans retinoic acid (atRA) has markedly improved outcome in acute promyelocytic leukemia (APL) but has had little clinical impact in other AML sub-types. Cell intrinsic mechanisms of resistance have been previously reported, yet the majority of AML blasts are sensitive to atRA in vitro. Even in APL, single agent atRA induces remission without cure. The microenvironment expression of cytochrome P450 (CYP)26, a retinoid-metabolizing enzyme was shown to determine normal hematopoietic stem cell fate. Accordingly, we hypothesized that the bone marrow (BM) microenvironment is responsible for difference between in vitro sensitivity and in vivo resistance of AML to atRA-induced differentiation. We observed that the pro-differentiation effects of atRA on APL and non-APL AML cells as well as on leukemia stem cells from clinical specimens were blocked by BM stroma. In addition, BM stroma produced a precipitous drop in atRA levels. Inhibition of CYP26 rescued atRA levels and AML cell sensitivity in the presence of stroma. Our data suggest that stromal CYP26 activity creates retinoid low sanctuaries in the BM that protect AML cells from systemic atRA therapy. Inhibition of CYP26 provides new opportunities to expand the clinical activity of atRA in both APL and non-APL AML.     

绝缘子调控基因的表达

绝缘子在调控真核基因时空特异表达的过程中起着至关重要的作用.它的主要功能是增强子阻断和异染色质屏障.已经有竞争、阻断和成环等模型描述其增强子阻断功能;而它的异染色质屏障功能主要是通过影响染色质组蛋白的翻译后修饰来实现.已经确定的绝缘子包括果蝇基因组中的染色质特化结构(specialized chromatin structures, scs)和scs、gypsy、鸡珠蛋白β基因座上游的DNaseⅠ高敏感位点cHS4以及小鼠或人Igf2/H19基因座上的印记控制区(imprinting control region, ICR)和DNA甲基化区域(DNA methylated regions, DMR)元件等.许多转录因子参与绝缘子的基因调控作用,例如脊椎动物中的CCCTC结合因子(CCCTC binding factor,CTCF).利用基因组学和生物信息学等方法,还可以在基因组中发现新的绝缘子元件.     

维甲酸诱导基因Ⅰ研究进展

维甲酸诱导基因Ⅰ(RIG-Ⅰ),能在多种细胞中被不同的刺激诱导表达,是RNA病毒致天然免疫的重要调控因子.概述其发现、诱导、结构、功能、机理及同源蛋白等的研究现状,并展望相关动向.     

Possible Role of Cyclic AMP in the Receptor-Mediated Regulation of Glycosyltransferase Activities in Neurotumor Cell Lines

Exposure of mouse neuroblastoma cell line N4TGl to opiates or [D-Ala2,D-Leu5] enkephalin produced a naloxone-reversible inhibition of cyclic AMP synthesis and prevented, in a concentration-dependent manner, the formation of both ganglioside GM2 (GalNAc-[NeuNAc]-Gal-Glc-ceramide) from GM3 (NeuNAc-Gal-Glc-ceramide) and ganglioside GM1 (Gal-GalNAc-[NeuNAc]-Gal-Glc-ceramide) from GM2 in cell-free extracts. In contrast, the receptor-mediated elevation of intracellular cyclic AMP levels by agents such as prostaglandin E1 (in the presence of isobutylmethylxanthine) or the addition of the cyclic AMP derivatives (dibutyryl cyclic AMP) markedly stimulated the activities of UDP-GalNAc:GM3,N-acetylgalactosaminyltransferase and UDP-Gal:GM2,galactosyltransferase. An overall increase in the synthesis of gangliosides more complex than GM3 was also observed in the mouse neuroblastoma x hamster brain explant hybrid cell line NCB-20 following elevation of cyclic AMP levels by treatment with serotonin and pargyline. The data presented support the hypothesis that cyclic AMP may have a role in the regulation of sialoglycosphingolipid biosynthesis.     

A Role for Myocilin in Receptor-Mediated Endocytosis

Myocilin is a broadly expressed protein that when mutated uniquely causes glaucoma. While no function has been ascribed to explain focal disease, some properties of myocilin are known. Myocilin is a cytoplasmic protein that also localizes to vesicles specifically as part of a large membrane-associated complex with properties similar to the SNARE machinery that function in vesicle fusion. Its role in vesicle dynamics has not been detailed, however myocilin intersects with the endocytic compartment at the level of the multivesicular body. Since internalized GPCRs are sorted in the multivesicular body, we investigated whether myocilin functions in ligand-dependent GPR143 endocytosis. Using recombinant systems we found that the kinetics of myocilin recruitment to biotinylated membrane proteins was similar to that of arrestin-3. We also co-localized myocilin with GPR143 and Arrestin-2 by confocal microscopy. However, wild-type myocilin differed significantly in its association kinetics and co-localization with internalized proteins from mutant myocilin (P370L or T377M). Moreover, we found that myocilin bound to the cytoplasmic tail of GPR143, an interaction mediated by its amino terminal helix-turn-helix domain. Hydrodynamic analyses show that the myocilin-GPR143 protein complex is >158 kD and stable in 500 mM KCl, but not 0.1% SDS. Collectively, data indicate that myocilin is recruited to the membrane compartment, interacting with GPCR proteins during ligand-mediated endocytosis and that GPCR signaling underlies pathology in myocilin glaucoma.     

肽核酸对基因调节作用的研究进展

肽核酸(PNA)是一类人工合成的核酸类似物,PNA与核酸链以Waston-Crick碱基配对方式稳定互补结合,具有高度的亲合性、稳定性、特异性特征,PNA能调节基因的复制、转录（或逆转录）和翻译过程,有着广泛的分子生物学效应,显示出其作为基因调节药物的应用潜力。     

Tumor Necrosis Factor Receptors in Neuroblastoma SKNBE Cells and Their Regulation by Retinoic Acid

Abstract: The human neuroblastoma cell line SKNBE can be differentiated either by serum removal or by adding to the culture medium different morphogens, for instance, retinoic acid (RA), cyclic AMP derivatives, and phorbol esters. Both the differentiated and undifferentiated cells express the two types of membrane tumor necrosis factor (TNF) receptors (TNFRs) of 55 and 75 kDa (p55 and p75 TNFR, respectively) and also their soluble forms. After RA addition the number of the surface TNFRs per cell is increased approximately twofold, but the kinetics of expression are different, depending on the receptor type. The level of the mRNAs of 2.4 and 4.2 kb, which, respectively, encode the p55 and p75 TNFRs, is also increased during the time course of differentiation, and the kinetics of their expression are biphasic. In contrast, the number of TNFRs and the level of their encoding mRNAs remain unchanged after exposure of the cells to both a phorbol and a cyclic AMP derivative.     

脱落酸与Em基因的表达调控

Em基因的表达受ABA诱导,干旱和盐胁通过增加ABA含量或改变植物细胞对ABA的敏感性而诱导Em基因的表达。植物Em基因启动子存在3个功能区:5′远端AT富集区通过影响转录调节表达量,作用类似于非专一性增强子;ABA应答元件ABRE在ABA存在的情况下与转录因子EmBP1相互作用能显著增强Em基因的表达;5′UTR可能通过转录后调控而影响最终表达水平 。     

Interplay of Protein Disorder in Retinoic Acid Receptor Heterodimer and Its Corepressor Regulates Gene Expression

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维甲酸对SK-N-SH细胞增殖和相关基因表达的影响

目的:研究维甲酸对SK-N-SH细胞的增殖和相关基因表达的影响.方法:通过苔盼蓝排除法绘制细胞生长曲线、流式细胞技术测定细胞周期、HE染色光镜观察细胞形态改变以及SABC免疫细胞化学梁色法观察维甲酸对SK-N-SH相关癌基因、抑癌基因表达的影响.结果:1μmol/LRA处理后,SK-N-SH细胞的增殖活动受到明显的抑制,处理第7天抑制率达36.16%;周期测定显示处理后出现明显的G0/G1期阻滞,由对照组的49.7%增加至62.7%,增加了26.2%;免疫细胞化学染色结果显示,处理后细胞癌基因c-myc、c-fos的表达较对照组明显降低,而抑癌基因p53、p27的表达则有所加强.结论:维甲酸能有效抑制SK-N-SH细胞的增殖活动,其对细胞的增殖抑制作用与RA下调c-myc、c-fos等癌基因以及上调p53、p27等抑癌基因的表达有关.