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目的探讨宫颈癌细胞中叶酸对DNA甲基转移酶1(DNMTl)和甲基化CpG岛结合蛋白2(MeCP2)表达的调节作用。方法采用体外实验研究方法,对宫颈癌细胞casl(i(HPVl6阳性)和C33A(HPV阴性)进行不同浓度(10、50、100、500、750、1000 I.tg/m1)叶酸干预,分别采用Western blot和real-time PCR方法检测两种细胞中DNMTl和MeCP2蛋白的表达量和mRNA水平。结果随着叶酸水平的升高,两种细胞的生长抑制率(C33A:r=0.984,Pr=0.978,P=0.002)和凋亡率(C33A:r=0.989,P<0.001;Caski:r=0.994,Pr=0.914,Pr=0.859,P=0.003)及MeCP2蛋白表达(C33A:r=0.830,P=0.005;Caski:r=0.981,P<0.001)均呈逐渐降低趋势,而DNMTl和MeCP2 mRNA的Ct比值在两种细胞中的变化均无统计学意义(P>O.05)。相同叶酸浓度下,DNMTl蛋白和mRNA表达水平在Caski细胞均较C33A细胞为高,而MeCP2蛋白和mRNA表达水平则在C33A细胞较Caski细胞普遍为高。结论补充叶酸可有效抑制宫颈癌细胞的增殖,促进凋亡,逆转DNMTl和MeCP2蛋白的异常表达;HPVl6感染与DNMTl功能异常对宫颈癌的发生可能有协同效应。 相似文献
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Background and Aim Asymmetric dimethylarginine(ADMA),an endogenous inhibitor of nitric oxide synthase(NOS),has been shown to be an independent predictor of coronary heart disease(CHD).Dimethylarginine dimethylaminohydrolase-2(DDAH2) promotes the metabolism of ADMA and plays a key role in formation of the atherosclerosis.We hypothesized that genetic variation inDDAH2 gene might alter the susceptibility to CHD.Methods We tested our hypothesis in a case-control studies.We used ahaplotype-tagging single nucleotide polymorphisms(SNP) approach to identify tag SNP in DDAH2.The SNP were genotyped by poly-merase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and ligase detection reaction(LDR)-sequencing in 1650patients with CHD and 1920 control subjects.Results Apromoter variant-449C/G(rs805305) and -1415G/A(rs2272592)in DDAH2 was identified in the region containing DDAH2.The frequency of those polymorphism were consistent with the lawof Har-dy-Weinberg.The frequency of rs805305 CG +GG or G allele was not significantly different between CHD and wild-type genotype(OR: 0.667,95%CI: 0.374 to 1.187,p>0.05).The frequency of rs2272592 GA +AA or A allele also showed no significant difference between CHD and wild-type genotype(OR: 1.420,95%CI: 0.899 to 2.242,p>0.05).No association was observed be-tween the DDAH2 variant and CHD.These results was independent of age,gender,hypertension,diabetes and hyperlipidemia.Conclusions Our results suggest that although DDAH2/ADMA pathway acts as a critical regulator of coronary atherosclerotic heartdisease,the DDAH2 common variant may not predict the susceptibility to CHD in Chinese population. 相似文献
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