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71.
《Ultrastructural pathology》2013,37(5):197-208
This study investigated the ultrastructural conformation changes of the chromatin in blood leukocytes of bipolar patients, versus normal controls, by using the phosphotungstic acid-hematoxylin (PTAH) block-staining method, modified for electron microscopy, and the immunohistochemical localization of the histone H1, by the immunogold method. These two methods are basically complementary. If histone H1 immunolabeling is used, it shows that the immunogold labeling on chromatin is different in the three phases of the illness, i.e., high in normothymia and low in depression as well as in mania. However, in this particular tissue fixation (4% paraformaldehyde-1% glutaraldehyde in 0,1 M phosphate buffer), the heterochromatin in the nuclei remains identical in the three phases of the illness. On the other hand, the PTAH method shows exactly the area of electron-lucent condensed chromatin, separate from the area of electron-dense, decondensed, chromatin. The present data confirmed that both the clinical state of depression as well as that of mania display activated lymphocytes and neutrophils with their characteristic relaxed de-condensed chromatin. On the contrary, the state of normothymia shows a reversion to the condensed state of the chromatin, as it is observed in the leukocytes of the normal controls. The ultrastructural conformations of the chromatin, revealed by the PTAH method, in combination with the histone H1 immunogold labeling, applied in blood leukocytes, supports the use of these two methods, as screening methods of choice in investigating blood biological markers in mental illness. 相似文献
72.
Yu‐Chen Han Zhong‐Liang Zheng Ze‐Hua Zuo Yan P Yu Rui Chen George C Tseng Joel B Nelson Jian‐Hua Luo 《The Journal of pathology》2013,230(2):184-193
Metallothioneins (MTs) are a group of metal binding proteins thought to play a role in the detoxification of heavy metals. Here we showed by microarray and validation analyses that MT1h, a member of MT, is down‐regulated in many human malignancies. Low expression of MT1h was associated with poor clinical outcomes in both prostate and liver cancer. We found that the promoter region of MT1h was hypermethylated in cancer and that demethylation of the MT1h promoter reversed the suppression of MT1h expression. Forced expression of MT1h induced cell growth arrest, suppressed colony formation, retarded migration, and reduced invasion. SCID mice with tumour xenografts with inducible MT1h expression had lower tumour volumes as well as fewer metastases and deaths than uninduced controls. MT1h was found to interact with euchromatin histone methyltransferase 1 (EHMT1) and enhanced its methyltransferase activity on histone 3. Knocking down of EHMT1 or a mutation in MT1h that abrogates its interaction with EHMT1 abrogated MT1h tumour suppressor activity. This demonstrates tumour suppressor activity in a heavy metal binding protein that is dependent on activation of histone methylation. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
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Emilie Montellier Fay?al Boussouar Sophie Rousseaux Kai Zhang Thierry Buchou Fran?ois Fenaille Hitoshi Shiota Alexandra Debernardi Patrick Héry Sandrine Curtet Mahya Jamshidikia Sophie Barral Hélène Holota Aurélie Bergon Fabrice Lopez Philippe Guardiola Karin Pernet Jean Imbert Carlo Petosa Minjia Tan Yingming Zhao Matthieu Gérard Saadi Khochbin 《Genes & development》2013,27(15):1680-1692
The conversion of male germ cell chromatin to a nucleoprotamine structure is fundamental to the life cycle, yet the underlying molecular details remain obscure. Here we show that an essential step is the genome-wide incorporation of TH2B, a histone H2B variant of hitherto unknown function. Using mouse models in which TH2B is depleted or C-terminally modified, we show that TH2B directs the final transformation of dissociating nucleosomes into protamine-packed structures. Depletion of TH2B induces compensatory mechanisms that permit histone removal by up-regulating H2B and programming nucleosome instability through targeted histone modifications, including lysine crotonylation and arginine methylation. Furthermore, after fertilization, TH2B reassembles onto the male genome during protamine-to-histone exchange. Thus, TH2B is a unique histone variant that plays a key role in the histone-to-protamine packing of the male genome and guides genome-wide chromatin transitions that both precede and follow transmission of the male genome to the egg. 相似文献
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目的:观察去乙酰化酶HDAC6特异性抑制剂Tubacin对MIN6细胞胰岛素分泌的影响,并探讨其可能机制。方法:用RT-PCR检测去乙酰化酶家族成员在MIN6细胞的表达,用免疫荧光技术观察HDAC6在小鼠胰岛和MIN6细胞内的定位;分别在5.6mmol/L和25mmol/L葡萄糖的DMEM中加和不加10μmol/LTubacin,用其处理MIN6细胞24h,收集上清,ELISA检测胰岛素浓度。同时用MTT法检测Tubacin对MIN6细胞活力的影响,RT-PCR检测上述处理条件下Insulin基因的表达情况。以Westernblot和免疫荧光技术检测Tubacin对MIN6细胞骨架蛋白α-tubulin乙酰化水平的影响。结果:MIN6细胞中各乙酰化酶家族成员mRNA的表达水平相差较大,其中HDAC6表达相对较高。HDAC6主要表达于小鼠胰岛B细胞及MIN6细胞胞浆中。在5.6imnol/L和25mmol/L葡萄糖条件下,Tubaein处理24h可以显著抑制胰岛素分泌,但不影响MIN6细胞活力。同时,在5.6mmol/L葡萄糖存在条件下Tubacin不影响胰岛素基因表达,在25mmol/L葡萄糖存在条件下Tubacin可轻度上调胰岛素基因表达。Westernblot和免疫荧光结果发现,Tubacin抑制胰岛素分泌的同时伴有α—tubulin乙酰化水平增加。结论:HDAC6抑制剂Tubacin可能通过增加MIN6细胞d.tubulin乙酰化水平,改变细胞骨架的活动度而抑制胰岛素分泌。 相似文献
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目的:利用化学发光方法和细胞筛选模型,检测新型组蛋白去乙酰化酶抑制剂( histone deacetylase inhibitor, HDACi)JZ005的抑制组蛋白去乙酰化酶(histone deacetylases,HDACs)的活性;建立氯化钴损伤的心肌细胞缺氧模型,初步探讨JZ005对缺氧损伤细胞的保护作用。方法采用脂质体转染法将含有p21启动子元件的荧光素酶报告基因真核表达载体pCI-p21-Luc转入到人胚肾细胞293中,用G418筛选获得稳定转染荧光素酶报告基因的单克隆细胞系;采用已报道的HDACi曲古抑菌素A( trichostatina A,TSA)为阳性对照,检测细胞筛选模型的稳定性;用HDACi化学发光检测试剂盒及上述细胞筛选模型测定JZ005抑制HDACs的活性;用不同浓度的JZ005处理氯化钴缺氧损伤的大鼠胚胎心肌细胞(H9c2),MTT法检测JZ005对缺氧损伤细胞的保护作用。免疫印迹法检测JZ005处理后正常及缺氧损伤心肌细胞组蛋白H3的乙酰化水平变化。流式细胞术检测JZ005对H9c2细胞缺氧损伤后凋亡的影响。结果建立含p21启动子元件荧光素酶报告基因的HDACi细胞筛选模型;JZ005能够显著抑制HDACs的活性,浓度50~400μmol/L,抑制率>50%。对缺氧损伤的心肌细胞具有明显保护作用,与对照组相比,细胞存活率提高38.33%、56.00%和35.20%,同时能够上调缺氧损伤心肌细胞组蛋白H3的乙酰化水平,拮抗缺氧损伤心肌细胞的凋亡,细胞凋亡数目从对照组的12.89%分别下降到给药组(25,50和100μmol/L)的6.63%、10.56%和8.89%。结论成功建立了HDACi的细胞筛选模型;JZ005作为一种新型的HDACi ,具有明显的保护心肌细胞拮抗缺氧损伤的作用,提示JZ005有可能开发成一种治疗缺氧损伤的药物。 相似文献
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