SENP3在疾病发生发展中作用的研究进展

小泛素样修饰蛋白(SUMO)特异性蛋白酶(SENP)能介导SUMO前体加工和去SUMO化修饰,是细胞内SUMO稳态维持的核心调控因子。SENP3是SENP家族成员之一,分布于核仁并优先催化靶蛋白的去SUMO2/3修饰;通过与靶蛋白结合并去SUMO化靶蛋白调节多种胞内蛋白功能。一旦SENP3的表达异常,便会引发一系列细胞异常活动,最终导致疾病的发生发展。本文对SENP3在疾病中的功能研究进展做一综述。     

核因子-κB信号通路中小泛素样修饰蛋白与2型糖尿病的关系

小泛素样修饰蛋白化是通过一系列小泛素样修饰蛋白(small ubiquitin-related modifier,SUMO)酶介导的生化级联反应将SUMO共价结合于靶蛋白的赖氨酸残基上,提高蛋白质稳定性,介导靶分子定位和功能调节的过程。经典通路κB抑制蛋白激酶(inhibitory proteinκB kinaseβ,IKKβ)/核因子κB(nuclear factorsκB,NF-κB)途径是炎性反应的关键信号转导通路。而NF-κB是公认的参与炎症和免疫反应的调节因子。研究发现,不仅NF-κB抑制蛋白(inhibitory protein,IκBa)的SUMO化修饰参与NF-kB信号通路的调节,而且SUMO酶可以直接介导NF-kB对靶基因的转录调控,某些蛋白也可能与SUMO化蛋白有相互作用。文中对SUMO修饰系统、SUMO循环及参与SUMO化循环的酶对NF-kB信号通路的转录调控及其与2型糖尿病相关性研究进行综述。     

小鼠窦前卵泡培养成熟后卵母细胞纺锤体的变化

目的小鼠窦前卵泡体外培养得到成熟卵母细胞,观察卵母细胞的染色体和纺锤体形态,分析其变化及原因。方法完整小鼠窦前卵泡培养12 d,得到的卵母细胞进行免疫荧光染色,共聚焦显微镜观察纺锤体和染色体的形态和分布。结果经过体外培养,得到GV、M I、MⅡ期卵母细胞分别占总数27.9%、37.2%、34.9%;GV期卵母细胞存在完整的染色质圆环,11.8%的M I期卵母细胞显示正常纺锤体和染色体;38.5%的MⅡ期卵母细胞显示正常的纺锤体和染色体。结论小鼠窦前卵泡经体外培养后能够得到成熟的MⅡ期卵母细胞,但是其效率较低。原因可能是卵母细胞骨架结构的异常使染色体分离障碍,部分卵母细胞停留于M I期;同时成熟卵母细胞的受精率低也与纺锤体异常有关。     

SUMO特异性蛋白酶家族的结构、分布、功能和调控

蛋白质的翻译后修饰对调节蛋白质的功能活性和定位以及调控细胞周期进程和细胞分化都起着非常重要的作用,其中小泛素样修饰蛋白(SUMO)化修饰是一个可以由SUMO特异性蛋白酶(SENPs)家族逆转的高度动态的过程。SENPs能够从与SUMO连接的靶蛋白上催化去除SUMO,以及从它的前体蛋白上裂解SUMO;同时,此家族部分成员还参与SUMO的成熟活化过程;因此,去SUMO化修饰对于调节SUMO连接蛋白的功能及活性与SUMO化同样重要。本文就SENPs家族的结构及生物学特性作一综述。     

SENP1与恶性肿瘤相关性的研究进展

类泛素蛋白修饰分子(SUMO)是一类小泛素样蛋白修饰物,蛋白SUMO化修饰是维持蛋白稳态的重要方式。SUMO特异性蛋白酶(SENP)是一类去SUMO化的水解酶,通过去SUMO化影响底物蛋白功能,参与调控细胞周期、细胞增殖和细胞凋亡等众多生物学过程。其中,SENP1在多数肿瘤组织中异常高表达,并通过影响多种信号途径促进肿瘤的发展。该文主要综述了低氧调控SENP1/缺氧诱导因子-1α(HIF-1α)影响肿瘤进展的机制,SENP1通过调节基质金属蛋白酶(MMP)-2、MMP-9及上皮细胞-间充质转化(EMT)过程参与肿瘤转移,SENP1与c-Myc信号通路相关,SENP1受miRNA调控机制及SENP1在肿瘤耐药及预后中的作用。深入研究SENP1调控肿瘤发生、发展作用和机制将为精准治疗提供新的靶点和策略。     

Synaptotagmin1影响小鼠卵母细胞纺锤体组装和稳定

目的:确定Synaptotagmin1(Syt1)对小鼠卵细胞纺锤体组装和稳定的影响。方法:免疫荧光法检测Syt1在小鼠卵母细胞发育不同时期的亚细胞定位。用紫杉醇处理小鼠MⅠ期卵母细胞,明确Syt1与微管动力的关系。注射Syt1特定的寡聚核苷酸降调卵母细胞中Syt1的表达,免疫荧光法检测Syt1降调后卵母细胞纺锤体的形态变化、染色体异常以及中心体蛋白γ-tubulin定位变化。结果:Syt1在卵母细胞减数分裂成熟的不同发育阶段都有表达,主要集中分布皮质区和MⅠ和MⅡ期纺锤体的两极。Syt1在MⅠ和MⅡ期与中心体相关蛋白γ-tubulin共定位。紫杉醇实验发现Syt1集中定位于星体和高度集中的微管两极。降调Syt1表达后,染色体排列紊乱,纺锤体组装异常比例升高,且大多数为无极、单极或者多级纺锤体,其次有拉长纺锤体和形态各异纺锤体。并影响微管组织中心相关蛋白γ-tubulin的正确定位。结论:Syt1可能作为一种微管组织中心相关蛋白调节纺锤体的组装稳定。     

小泛素相关修饰物化修饰在卵巢生理与病理过程中的作用研究进展

蛋白质翻译后修饰是细胞的重要调控机制之一,包括磷酸化、甲基化、乙酰化、泛素化和小泛素相关修饰物（SUMO）化修饰等,目前SUMO化修饰成为近年来卵泡发育和卵巢疾病的研究热点,并发现其参与了调节基因转录、细胞周期、维持染色质结构和基因组稳定以及DNA损伤修复等过程。SUMO化修饰是动态可逆的,去SUMO化修饰过程由SUMO特异性蛋白酶介导。随着研究的深入,发现在卵巢中SUMO化修饰主要通过调节细胞增殖、凋亡和DNA损伤修复而影响卵泡发育。因此,研究SUMO化修饰与卵泡发育的关系能为阐明卵巢疾病的发病机制及诊治提供新思路。     

染色体和遗传

061474 性染色体异常核型37例细胞遗传学分析；061475 17例9号染色体臂间倒位遗传学分析；061476 排卵后老化对卵母细胞姐妹染色单体平衡性早分离的影响;061477 产前诊断48，XY，＋21，＋22和48，XY，＋7，＋8各1例；061479 46，XY，t（1；17）（q23；q25）伴流产畸胎1例。     

乳腺癌相关蛋白的类泛素化修饰研究进展

类泛素蛋白SUMO在调节蛋白质的稳定性和功能中起着关键的作用,此外它还能够通过对转录因子及其共调节因子的修饰来调节蛋白质相互作用、蛋白亚细胞定位、蛋白质二聚化及调控基因转录等.本文通过总结SUMO系统对雌激素信号通路蛋白的修饰作用,以及其他乳腺癌相关蛋白的修饰作用,阐释其在乳腺癌发生发展中的重要功能.     

ASPM在恶性肿瘤中的研究进展

异常纺锤体样小头畸形相关蛋白(ASPM)基因是最常见的常染色体隐性小头畸形突变基因.其主要功能包括正确引导有丝分裂中纺锤体向两极运动以及维持细胞质的均等分裂,在有丝分裂纺锤体调节和有丝分裂过程的协调中发挥作用,并调控细胞周期进展.ASPM在各种恶性肿瘤组织高表达,影响恶性肿瘤的发生、发展及预后.同时,ASPM还参与肿瘤...     

PTTG ESP1在A549 SPC-A-1细胞株S G2/M期的表达

目的探讨PTTG(pituitary tumortransforming gene)、ESP1(estradiol-stimulated protein 1)在A549、SPC-A-1细胞S、G/M期的表达.方法用双胸苷同步化法同步化A549、SPC-A-1细胞及MRC-5细胞,分别收集S、G2/M期总RNA,做Realtime PCR.结果PTTG在A549细胞和SPC-A-1细胞的S期表达比G2/M期表达高,在MRC-5细胞的在S、G2/M期中P1TG均无表达;ESP1在A549细胞与SPC-A-1细胞及MRC-5细胞的S期表达均比G2/M期表达低.结论PTTG在MRC-5的S、G2/M期都无表达,在A549、SPC-A-1的S期比G2/M期表达增高,提示肿瘤细胞的染色体非整倍体与PTTG的表达增高有关;ESP1在MRC-5和A549、SPC-A-1的S期比G2/M期表达低,说明细胞中姐妹染色体的分离主要依靠于ESP1在G2/M期被激活,而导致姐妹染色体的分离.     

LIMK1 activity is required for MTOC localization and spindle bipolarity establishment during meiosis in mouse oocytes

Aneuploid embryo generally leads to infertility,spontaneous abortion and birth defects,mainly resulting from abnormal chromosome segregation during maternal oocytes meiosis.Chromosome division is conducted by bipolar spindle which formed through an acentrosomal way,dependent on a unique microtubule organizing center(MTOC)in mammalian oocytes,however,the molecular composition and functional regulation of MTOC is still not fully explored.LIM kinases 1(LIMK1)is a conserved serine/threonine kinase,a major regulator of actin and microtubule dynamics,involved in microtubule stability and spindle positioning during mitosis.So far little is known about LIMK1 protein expression and its roles in oocytes during meiosis.We reported here the protein expression and sub-cellular distribution of LIMK1 in mouse oocytes during meiosis.Western blot procedure detected high and stable expression of LIMK1 in mouse oocytes from germinal vesicle(GV)stage to metaphase II(MII).In contrast,activated LIMK1(phosphorylated at Thr508,p LIMK1Thr508)was only observed after germinal vesicle breakdown(GVBD),and gradually increased with peak levels at metaphase I(MI)and MII.Immunofluorescence analysis showed that LIMK1 was co-localized with microtubules on the whole spindle structure,while p LIMK1Thr508wasconcentrated with key components of MTOC,pericentrin and-Tubulin,on spindle poles in mouse oocytes.Inhibition of LIMK1 activity by BMS3,a specific ATPase competitive inhibitor,distroyed the formation of bipolar spindle structure,disturbed MTOC integrity and MTOC proteins recruitment to spindle poles.Moreover,LIMK1 inhibition caused chromosome misalignment and meiotic progression arrest at MI stage.Therefore,LIMK1 activity is required for formation and maintenance of bipolar spindle in mouse oocytes,importantly,p LIMK1T508is MTOC-associated protein,involved in establishment and positioning of MTOC.     

CYTOGENETIC STUDY ON PERIPHERAL LYMPHOCYTES IN TROPHOBLASTIC DISEASES

The frequency of sister chromatid exchanges and chromosomal aberrations of peripheral lymphocytes (i.e., subploid, hyperploid, tetra- ploid, breakage, fragmentation) were studied in 20 cases of hydatidiform mo,le, 23 cases of il:- vasive mole, 22 cases of choriocarcinoma, and 20 normal controls. The. sister chromatid ex- change frequency was 5.74+01.69 per metaphase in normal women, and 6.84+1.56 in hydatidiform mole, 11.49+2.24 in invasive mole, and 11.37+1.90 in choriocarcinoma. The frequency of chromo- somal aberrations was highest in choriocar- cinoma, and lowest in normal controls, with hydatidiform mole and invasive mole second and third. Statistically significant differences were found in these Z indices in the 4 groups.     

Cytogenetic findings in persons living near the Love Canal

Cytogenetic analyses were performed on peripheral blood from 46 present or past residents of the area surrounding Love Canal, a former dump site for chemical wastes in Niagara Falls, NY. Participants included 17 persons in whom cytogenetic analyses had been performed in 1980 and 29 persons who had been living in 1978 in seven homes that directly adjoined the canal and in which environmental tests showed elevated levels of chemicals spreading from the canal. Frequencies of chromosomal aberrations and of sister chromatid exchange (SCE) did not differ significantly from control levels. For all participants, cigarette smoking was associated with an increase in sister chromatid exchange frequency.     

染色体技术在相关疾病临床诊断中的应用

目的：探讨染色体技术对临床诊断某些疾病的应用价值。方法：应用常规外周血淋巴细胞染色体标本制备、G显带、C显带技术，姐妹染色单体交换（SCE）技术、染色体断裂试验、骨髓染色体标本制备技术。结果：304例患者中检出异常核型39例，异常染色体核型率为12．72％。其中罗伯逊易位携带者4例,Klinefelter综合征患者11例，Turner综合征患者1例，完全型睾丸女性化综合征患者（46，XY）1例，21三体患者16例，Ph染色体阳性3例，范可尼氏贫血患者3例。结论：染色体技术是某些遗传性疾病临床诊断必不可少的手段。异常染色体的检出对患者的治疗、预后及优生、优育、优教都有重要指导意义。     

In vitro Antigenotoxicity of Ulva rigida C. Agardh （Chlorophyceae） Extract against Induction of Chromosome Aberration,Sister Chromatid Exchange and Micronuclei by Mutagenic Agent MMC

Objective To determine the in vitro possible clastogenic and cytotoxic activities of Ulva rigida crude extracts （URE）, and identify their antigenotoxic and protective effects on chemotherapeutic agent mitomycine-C （MMC）. Methods Anti-clastogenic and anti-genotoxic activities of Ulva rigida crude extracts （URE） were studied using chromosome aberration （CA）, sister chromatid exchange （SCE）, and micronuclei （MN） tests in human lymphocytes cultured in vitro. Results The chromosome aberration, sister chromatid exchange or micronuclei tests showed that URE at concentrations of 10, 20, and 40 lag/mL had no clastogenic activity in human lymphocyte cell culture. Three doses of URE significantly decreased the number of chromosomal aberrations and the frequencies of SCE and MN when compared with the culture treated with MMC （P〈0.0001）. Conclusion Although URE itself is not a clastogenic or cytotoxic substance, it possesses strong antigenotoxic, anti-clastogenic, and protective effects on MMC in vitro.     

Pallister-Killian syndrome: meiosis II non-disjunction may be the first step in the formation of isochromosome 12p

Pallister-Killian syndrome （PKS） is a rare and sporadic genetic disorder due to tissue-limited mosaicism for supernumerary isochromosome 12p（i（12p））, which is usually absent or at low-level mosaicism in cultured lymphocytes but present in fibroblasts. PKS was first described in adults by Pallister in 19771 and later in children by Killian and Teschler-Nicola in 1981.2 An accurate incidence is unknown. It is clinically characterized by profound mental retardation, seizures,hypotonia, supernumerary nipples, pigmentary dysplasia,diaphragmatic hernia, ＂coarse＂ face, including prominent forehead with sparse anterior scalp hair, hypertelorism,short nose with anteverted nares, flat nasal bridge, long philtrum, cleft palate and short neck. Here we report a patient with PKS, who is the first confirmed case with PKS in mainland China. Molecular analysis was performed to explore the formation mechanism of i（12p）.The results suggest that the maternal meiosis Ⅱ sister chromatid non-disjunction was likely the first step in the formation of i（12p）, followed by postzygotic mitotic centromeric misdivision.     

食用吉林地区棋盘村“污染白菜”居民的姐妹染色单体互换和染色体畸变

本实验对吉林地区102厂附近棋盘村食用“污染白菜”的健康居民,进行SCE和染色体畸变的观察。结果表明,食用“污染白菜”和食用非污染白菜居民的SCE和染色体畸变率均无统计学差异(P>0.05)。     

岩参诱发NIH小鼠微核、人类染色体畸变和SCE频率的实验研究

岩参(Bergenia purpurascens)又名岩白菜,为虎耳草科植物,主产于西南地区,生长在海拔1000～3000m背阴面岩坡上.按中药炮制加工工艺将岩参制成药片,在四川省阆中、盐亭两县对食管癌高发区的食管上皮细胞增生和上消化道炎症患者1万多人进行长达5年多的治疗观察,治愈率达88.7％,表明岩参对上消化道炎症疗效显著,是一种具有开发前景的新药.作者在对岩参进行了一系列急、慢性毒性实验的基础上,进行微核试验、染色体畸变、SCE频率和DNA合成抑制实验,为岩参的进一步开发应用提供了理论依据.     

川乌不同炮制品提取物的致突变与抗突变作用研究

采用小鼠骨髓嗜多染红细胞微核(MN)实验、小鼠骨髓细胞姊妹染色单体交换(SCE)实验及染色体畸变(CA)实验,探讨蜜炙川乌醇沉提取物、蜜炙川乌提取物与药典法制川乌提取物的体内致突变与抗突变作用.结果表明川乌各炮制品提取物均无致突变性,各药对环磷酰胺(CP)引起的昆明种小鼠骨髓嗜多染红细胞MN、骨髓细胞SCE和CA有显著的抑制作用,其中蜜炙川乌醇沉提取物和蜜炙川乌提取物的抗突变作用优于药典法制川乌提取物.提示制川乌对由环磷酰胺引起的遗传损伤有着明显的拮抗作用,川乌经蜜炙后其抗突变性有一定增强.