Kocic Gordana, Cukuranovic Jovana, Stoimenov Tatjana Jevtovic, Cukuranovic Rade, Djordjevic Vidosava, Bogdanovic Dragan, Stefanovic Vladisav
Faculty of Medicine, Institute of Biochemistry, University of Nis , Nis , Serbia .
Ren Fail. 2014 Aug;36(7):1078-82. doi: 10.3109/0886022X.2014.917562. Epub 2014 May 21.
Abstract Background: Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial nephropathy present in the Danube river regions in several Balkan countries. There appears to be a polygenic susceptibility to the disease in interaction with multiple environmental factors (aristolochic acid, ochratoxin A). In a previous study SEC61G, IL17RA, HDAC11 proved to be differently methylated throughout all patient-control pairs of BEN patients from Serbia and Bulgaria. Emerging connections between DNA methylation and histone acetylation prompted the present study on histone acetylation in patients with BEN.
The study involved 39 patients with BEN, and 39 controls collected from non-endemic regions in Serbia. The EpiSeeker Histone H3 and H4 Total Acetylation Detection colorimetric Kits and specific acetylated at lysine 18 H3K18 and H3K36 acetylated at lysine 36 detection kits were used.
It was documented that total H4 histone acetylation level was increased significantly, while total H3 histone acetylation did not differ significantly. Specific histone structure and functional properties may be affected by the observed derangement of H3 histone acetylation pattern, since H3K36 site was significantly more acetylated, while H3K18 tended to be less acetylated than in control subjects. Multiple regression analysis revealed a statistically significant relationship between H4, H3T and H3K36 in BEN patients.
This preliminary study suggests that the acetylation of histone lysine residues was detectable and found increased at specific sites of H3 and total H4 histones isolated from urothelial cells of patients with BEN. Having in mind a possible mechanism and biological role of epigenetic chromatin modification in urothelial tumor development they obtained results may open opportunity for selective therapeutic interventions in patients with BEN.
摘要 背景：巴尔干地方性肾病（BEN）是一种慢性肾小管间质性肾病，存在于几个巴尔干国家的多瑙河地区。该病似乎存在多基因易感性，并与多种环境因素（马兜铃酸、赭曲霉毒素A）相互作用。在之前的一项研究中，SEC61G、IL17RA、HDAC11在塞尔维亚和保加利亚的所有BEN患者病例对照对中显示出不同的甲基化情况。DNA甲基化与组蛋白乙酰化之间新出现的联系促使了本研究对BEN患者组蛋白乙酰化情况进行研究。
该研究纳入了39例BEN患者以及从塞尔维亚非流行地区收集的39例对照。使用了EpiSeeker组蛋白H3和H4总乙酰化检测比色试剂盒以及赖氨酸18位点特异性乙酰化的H3K18和赖氨酸36位点乙酰化的H3K36检测试剂盒。
记录显示，H4组蛋白总乙酰化水平显著升高，而H3组蛋白总乙酰化无显著差异。由于H3K36位点的乙酰化显著增加，而H3K18的乙酰化程度相较于对照受试者趋于降低，因此观察到的H3组蛋白乙酰化模式紊乱可能会影响特定的组蛋白结构和功能特性。多元回归分析显示，BEN患者中H4、H3T和H3K36之间存在统计学上的显著关系。
这项初步研究表明，从BEN患者尿路上皮细胞分离的H3组蛋白和H4组蛋白的特定位点可检测到组蛋白赖氨酸残基的乙酰化，且发现其增加。考虑到表观遗传染色质修饰在尿路上皮肿瘤发生中的可能机制和生物学作用，他们所获得的结果可能为BEN患者的选择性治疗干预提供机会。
