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Epigenetic control of early neurodegenerative events in diabetic retinopathy by the histone deacetylase SIRT6
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Ada Yeste Francisco J. Quintana Debra Toiber Raul Mostoslavsky Dafne M. Silberman 《Journal of neurochemistry》2018,144(2):128-138
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Cheng-En Hu Yong-Chao Liu Hui-Dong Zhang Guang-Jian Huang 《Biochemical and biophysical research communications》2014
Gastric carcinoma is the fourth most common cancer worldwide, with a high rate of death and low 5-year survival rate. However, the mechanism underling gastric cancer is still not fully understood. Here in the present study, we identify the RNA-binding protein PCBP2 as an oncogenic protein in human gastric carcinoma. Our results show that PCBP2 is up-regulated in human gastric cancer tissues compared to adjacent normal tissues, and that high level of PCBP2 predicts poor overall and disease-free survival. Knockdown of PCBP2 in gastric cancer cells inhibits cell proliferation and colony formation in vitro, whereas opposing results are obtained when PCBP2 is overexpressed. Our in vivo subcutaneous xenograft results also show that PCBP2 can critically regulate gastric cancer cell growth. In addition, we find that PCBP2-depletion induces apoptosis in gastric cancer cells via up-regulating expression of pro-apoptotic proteins and down-regulating anti-apoptotic proteins. Mechanically, we identify that miR-34a as a target of PCBP2, and that miR-34a is critically essential for the function of PCBP2. In summary, PCBP2 promotes gastric carcinoma development by regulating the level of miR-34a. 相似文献
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组蛋白去甲基化酶KDM7家族包括KDM7A、KDM7B、KDM7C三种蛋白,主要通过去除与转录沉默相关的特定组蛋白赖氨酸甲基化修饰,进而对基因转录发挥调控作用。目前,对KDM7家族的研究主要集中于其在神经分化、肿瘤发生发展等过程中的作用,而对其在脑神经疾病中的作用却知之甚少。本文从该蛋白家族表观遗传调控机制、结构生物学及其在脑神经疾病中的作用等方面进行了综述,以期为研究其在脑神经疾病中的功能机制提供参考,为理解脑神经疾病分子病理机制以及探索基于该机制的有效治疗靶点带来新的启示。 相似文献
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目的探讨硫化氢(H2S)对阿霉素(DOX)诱导的H9c2细胞损伤的影响及其作用机制。
方法H2S对DOX心肌毒性保护作用的实验分组为:对照组(Control组),5?μmol/?L DOX处理组(A组),5?μmol/L DOX和400?μmol/L NaHS共同处理组(B组),400?μmol/L NaHS单独处理组(C组),5?μmol/L DOX、400?μmol/L NaHS和15?μmol/L Sirtinol共同处理组(D组),15?μmol/L Sirtinol单独处理组(E组)。SIRT1是否参与H2S抗DOX心肌毒性作用机制的实验分组为:对照组(Control组),5?μmol/L DOX处理组(F组),5?μmol/L DOX和400?μmol/L NaHS共同处理组(G组),5?μmol/L DOX、400?μmol/L NaHS和15?μmol/L Sirtinol共同处理组(H组),15?μmol/L Sirtinol单独处理组(I组)。使用MTT法检测细胞活力;Elisa法检测细胞MDA以及SOD水平;DCFH-?DA荧光探针法检测ROS水平;采用Western Blot法检测SIRT1蛋白表达。使用单因素方差分析法进行统计学分析。
结果NaHS预处理可抑制DOX导致的H9c2细胞活力下降:Control组,A组、B组、C组细胞活力分别为100﹪、(54.58±1.58)﹪、(85.05±4.31)﹪、(100.22±4.46)﹪ (F = 134.9,P < 0.001)。NaHS预处理可减弱DOX引起的H9c2细胞ROS、MDA水平的增加以及SOD水平的降低:Control组的ROS、MDA和SOD水平分别是100﹪、(34.18±1.56) μmol/g、(53.69±1.44) U/?mg;A组的ROS、MDA和SOD水平分别是(174.90±12.65)﹪、(72.65±2.66) μmol/g、(31.80±2.05) U/?mg;B组的ROS、MDA和SOD水平分别是(126.08±6.25)﹪、(44.59±1.92) μmol/g、(48.06±1.56) U/mg;C组的ROS、MDA和SOD水平分别是(91.86±1.66)﹪、(32.93±1.56)?μmol/?g、(55.93±1.58)?U/?mg (F?= 83.26,P < 0.001;F = 271.4,P < 0.001;F = 127.0,P < 0.001)。F组(6、12、24?h)H9c2细胞SIRT1蛋白表达水平分别是(0.45±0.03)、(0.27±0.02)、(0.25±0.03),较Control组(1.00±0.00)降低(F = 611.1,P < 0.001)。本研究还发现,NaHS预处理H9c2细胞能阻止DOX引起的SIRT1蛋白表达下调:Control组、F组、G组、H组的SIRT1蛋白表达水平分别是(1.00±0.00)、(0.31±0.03)、(0.60±0.04)、(1.09±0.09)(F = 123.4,P?0.001)。SIRT1抑制剂Sirtinol预处理能明显逆转H2S对DOX诱导的H9c2细胞活力降低的抑制作用:Control组,F组、G组、H组、I组细胞活力分别为100﹪、(54.58±1.58)﹪、(85.37±3.62)﹪、(71.11±2.11)﹪、(97.53±1.45)﹪ (F = 238.2,P < 0.001)。Sirtinol预处理可明显逆转H2S对DOX导致的H9c2细胞ROS和MDA含量增加及SOD水平降低的抑制作用:Control组的ROS、MDA和SOD水平分别是100﹪、(35.84±2.22)μmol/?g、(53.03±3.16) U/mg;F组的ROS、MDA和SOD水平分别是(184.6±11.33)﹪、(74.78±5.30)μmol/g、(29.26±0.85)U/mg;G组的ROS、MDA和SOD水平分别是(126.5±7.57)﹪、(41.95±3.43)μmol/g、(52.61±2.26)U/mg;H组的ROS、MDA和SOD水平分别是(174.7±5.50)﹪、(67.69±1.52) μmol/g、(35.33±1.95) U/mg,I组的ROS、MDA和SOD水平分别是(98.03±2.86)﹪、(37.66±2.49)μmol/g、51.14 U/mg(F = 112.0,P < 0.001;F = 93.73,P < 0.001;F = 84.92,P < 0.001)。
结论H2S通过调控SIRT1抑制DOX诱导的H9c2细胞损伤。 相似文献
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《Cell reports》2023,42(8):112939
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Gliomas can diffuse into the normal brain and this invasion of glioma cells involves modification of receptor-mediated adhesive properties of tumor cells, degradation and remodeling of extracellular matrix by tumor-secreted metalloproteinase (MMPs) such as MMP-2, consequently creating an intercellular space for invasion of glioma cells. BmK CT, one of the key toxins in scorpion Buthus martensii Karsch venom, is a novel blocker of the chloride ion channel and MMP-2. In this report, a recombinant plasmid pEGFP-N1-BmK CT was constructed and characterized by in vitro studies. The results showed that pEGFP-N1 mediated BmK CT expression displayed a high activity in suppressing cell migration via MMP-2. The potential therapeutic effect of pEGFP-N1 mediated BmK CT against rat glioma C6 cells was assessed and its potential mechanism was elucidated. It represented an approach for developing a novel therapeutic agent—recombinant plasmid pEGFP-N1-BmK CT as an efficient and powerful adjuvant. 相似文献
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Regulation of SIRT6 protein levels by nutrient availability 总被引:2,自引:0,他引:2
Kanfi Y Shalman R Peshti V Pilosof SN Gozlan YM Pearson KJ Lerrer B Moazed D Marine JC de Cabo R Cohen HY 《FEBS letters》2008,582(5):543-548
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Knockdown or inhibition of SIRT2 enhances biological stress-tolerance. We extend this phenotype showing that SIRT2 knockdown reduces anoxia-reoxygenation injury in H9c2 cells. Gene array analysis following SIRT2 siRNA knockdown identifies 14-3-3 zeta as the most robustly induced gene. SIRT2 knockdown evokes induction of this chaperone, facilitating cytosolic sequestration of BAD with a corresponding reduction in mitochondrial BAD localization. Concurrent siRNA against SIRT2 and 14-3-3 zeta abolishes the SIRT2-depleted cytoprotective phenotype. SIRT2 functions to moderate cellular stress-tolerance, in part, by modulating the levels of 14-3-3 zeta with the concordant control of BAD subcellular localization. 相似文献
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Kai Sun Xuan Wang Na Fang Ao Xu Yao lin Xiaofang Zhao Adil J. Nazarali Shaoping Ji 《Journal of cellular and molecular medicine》2020,24(13):7439-7450
SIRT2 is a NAD+‐dependent deacetylase that deacetylates a diverse array of protein substrates and is involved in many cellular processes, including regulation of inflammation. However, its precise role in the inflammatory process has not completely been elucidated. Here, we identify heat‐shock protein 90α (Hsp90α) as novel substrate of SIRT2. Functional investigation suggests that Hsp90 is deacetylated by SIRT2, such that overexpression and knock‐down of SIRT2 altered the acetylation level of Hsp90. This subsequently resulted in disassociation of Hsp90 with glucocorticoid receptor (GR), and translocation of GR to the nucleus. This observation was further confirmed by glucocorticoid response element (GRE)‐driven reporter assay. Nuclear translocation of GR induced by SIRT2 overexpression repressed the expression of inflammatory cytokines, which were even more prominent under lipopolysaccharide (LPS) stimulation. Conversely, SIRT2 knock‐down resulted in the up‐regulation of cytokine expression. Mutation analysis indicated that deacetylation of Hsp90 at K294 is critical for SIRT2‐mediated regulation of cytokine expression. These data suggest that SIRT2 reduces the extent of LPS‐induced inflammation by suppressing the expression of inflammatory factors via SIRT2‐Hsp90‐GR axis. 相似文献