检索结果-南通市图书馆

Epigenetic modification enzymes: catalytic mechanisms and inhibitors

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2013年第3期3卷 141-149页

作者： Duo Lu Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Epigenetic modifications alter chromatin structures and consequently affect transcription and cellular functions.Major epigenetic markers include DNA methylation and histone acetylation and methylation.The modifications are reversible and are achieved in aid of relative enzymes.Much effort has been directed at the understanding of the chemical mechanisms of individual catalytic reactions,which can serve as a foundation for inhibitor development.Among the many methods deployed,structural studies have proven the most effective for understanding enzyme-mediated modifications and have provided support for the development of lead-candidate drug inhibitors.This review briefly summarizes the existing knowledge on the catalytic mechanisms of the major epigenetic modification enzymes,with an emphasis on the structural information and inhibitors of these enzymes.

关键词： Epigenetic modification histone acetylation histone methylation DNA methylation Catalytic mechanism Inhibitor

Implications of the gene balance hypothesis for dosage compensation

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Frontiers in Biology 2011年第2期6卷 118-124页

作者： James A.BIRCHLER Lin SUN Ryan DONOHUE Abhijit SANYAL Weiwu XIE Division of Biological Sciences University of Missouri ColumbiaMO 65211USA

Dosage compensation refers to the equal expression between the sexes despite the fact that the dosage of the X chromosome is different in males and females.In Drosophila there is a twofold upregulation of the single male X.In triple X metafemales,there is also dosage compensation,which occurs by a two-thirds downregulation.There is a concomitant reduction in expression of many autosomal genes in metafemales.The male specific lethal(MSL)complex is present on the male X chromosome.Evidence is discussed showing that the MSL complex sequesters a histone acetyltransferase to the X chromosome to mute an otherwise increased expression by diminishing the histone acetylation on the autosomes.Several lines of evidence indicate that a constraining activity occurs from the MSL complex to prevent overcompensation on the X that might otherwise occur from the high level of acetylation present.Together,the evidence suggests that dosage compensation is a modification of a regulatory inverse dosage effect that is a reflection of intrinsic gene regulatory mechanisms and that the MSL complex has evolved in reaction in order to equalize the expression on both the X and autosomes of males and females.

关键词： inverse dosage effect male specific lethal complex histone acetylation metafemales

Linking Cellular Metabolism to Epigenetics in Melanoma

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

International Journal of Dermatology and Venereology 2021年第3期4卷 168-173页

作者： Wei-Nan Guo Chun-Ying Li Department of Dermatology Xijing HospitalThe Fourth Military Medical UniversityXi’anShaanxi 710032China

Melanoma originates from epidermal melanocytes and is the most malignant form of skin cancer,with an increasing incidence worldwide.In addition to the known pathological mutations in melanoma,the remodeling of epigenetic modification has recently been documented to orchestrate the malignant behaviors of tumor cells and anti-tumor immunity,emerging as an irreversible tumorigenic event that is more preventable and treatable with medications.As a hallmark characteristic of cancer,the disorder of cellular metabolism is also greatly implicated in tumor carcinogenesis and development.Accumulating evidence has revealed the close linkage between metabolism and epigenetics in multiple biological activities.In the pathogenesis of melanoma,the findings of other groups and our laboratory highlight the pivotal role of autophagy,mitochondrial function,and the oncometabolite acetyl-CoA,as well as their epigenetic modification.Targeted metabolism-associated epigenetic modulation might be a novel approach for melanoma therapy in the future.

关键词： melanoma metabolism epigenetics autophagy histone acetylation miRNAs lipid metabolism targeted therapy

Low expression programming of angiotensin receptor Ⅱ mediated pancreatic β cell dysfunction and glucose intolerance in prenatal dexamethasone-exposed female rats

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

中国药理学与毒理学杂志 2019年第10期 757-758页

作者： KOU Hao GUI Shu-xia DAI Yong-guo Guo Yu WANG Hui Department of Pharmacy Zhongnan Hospital Department of Pharmacology School of Basic Medical SciencesWuhan University

OBJECTIVE To explore the intrauterine programming mechanism of pancreatic β cell dysfunction in prenatal dexamethasone-exposed（PDE） female adult offspring rats from the perspective of angiotensinⅡ receptor type 2（AT2 R） expression. METHODS Pregnant rats were subjected to the control, low-dose(0.2 mg·kg;·d;)[PDE（L）] and high-dose(0.8 mg·kg;·d;) [PDE（H）] of dexamethasone exposure groups. The subcutaneous injection of dexamethasone or equal volume of vehicle were conducted from gestational day（GD） 9 to 20. Some dams were sacrificed to obtain female fetal rats on GD20 and the remains were sacrificed in the postnatal week（PW） 28. Pancreatic morphometry, blood glucose-insulin phenotype and the expressions of genes related to insulin biosynthesis were examined. The rat insulinoma（INS-1）cells were treated with 4-100 nmol·L;of dexamethasone to verify its effects on insulin secretion. RESULTS The serum insulin levels, β cell mass and pancreatic insulin gene expressions of fetuses in the PDE groups on GD20 were lower than those in the control group. Meanwhile,the histone 3 lysine 27 acetylation（H3 K27 ac） levels in the AT2R promoter region as well as the gene expressions were reduced in the PDE groups when compared with the controls. These alterations could be maintained until PW28. Female adult offspring in the PDE groups presented hyperglycemia and glucose intolerance. PDE increased the gene expressions of glucocorticoid receptor（GR） and histone deacetylase 2（HDAC2） in both fetal pancreas on GD 20 and the INS-1 cells. Dexamethasone enhanced the interaction between GR and HDAC2 proteins as well as the binding of GR/HDAC2 complex to the AT2R promoter region in vitro. Moreover, overexpression of AT2R could reverse the suppression of insulin secretion and gene expression induced by dexamethasone in vitro,and both GR antagonist and histone deacetylase abolished the decreased H3K27 ac level and gene expression of AT2R. CONCLUSION Impairment of pancreatic βcell morphological development and insulin biosynthesis in utero induced

关键词： dexamethasone pancreatic β cell angiotensin receptor Ⅱ histone acetylation

Sulfatide Interaction with BRD1 Promotes Integrin αV Gene Expression

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Sulfatide Interaction with BRD1 Promotes Integrin αV Gene E...

中国生物化学与分子生物学会2016年全国学术会议

作者： QIAN QIAN CAI YI WEI DONG BING QI XIAO TING SHAO RONG WANG ZHONG YI CHEN BAO MEI HE HE YANG XU XING ZHONG WU Department of Biochemistry and Molecular Biology Shanghai Medical College Fudan University Key Lab of Glycoconjugate Research Ministry of Public Health Yu Ying Hospital Wenzhou Medical University

IntegrinαV is important in promotion of anchorage independence,angiogenesis and cancer metastasis,but its regulation is not well understood especially in hepatocellular carcinoma(HCC).Here we show that high integrinαV expression was closely associated with poor prognosis of patients with HCC and sulfatide activated integrinαV transcription through

关键词： bromodomain containing protein 1 sulfatide histone acetylation

ANGPTL4 facilitates the symbiosis between fusobacterium nucleatum and colorectal cancer cells bt promoting glycolysis

在线全文

cnki会议

学校读者我要写书评

暂无评论

ANGPTL4 facilitates the symbiosis between fusobacterium nucl...

2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青...

作者： Xin Zheng Rui Liu Chenchen Zhou Haopeng Yu Wanyi Luo Jianhui Zhu Jiaxin Liu Zhe Zhang Na Xie Xian Peng Xin Xu Lei Cheng Quan Yuan Canhua Huang Xuedong Zhou State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases West China Hospital of Stomatology Sichuan University West China Biomedical Big Data Center West China Hospital/School of Medicine Sichuan University State Key Laboratory of Biotherapy and Cancer Center West China Hospital and West China School of Basic Medical Sciences & Forensic Medicine Sichuan University

Objective: Fusobacterium nucleatum is linked to the development, metastasis and chemoresistance of colorectal cancer（CRC）. Numerous clinical and animal studies reveals an enrichment of F. nucleatum in the tumor tissue compared with adjacent normal tissue. Nonetheless, the mechanism underlies the colonization and persistence of F. nucleatum in CRC tissue is not fully clarified.Design: The mechanism of how F. nucleatum stimulates glycolysis activity of CRC cells and facilities its own colonization was investigated in vitro and confirmed with the Cancer Genome Atlas（TCGA）datasets, clinical tissues, and a xenograft model. The relationship between histone acetylation,ANGPTL4 induction, glycolysis activity of CRC cells and F. nucleatum persistence were further elucidated in vitro and in vivo.Results: We demonstrated that F. nucleatum infection remarkably promoted glucose uptake and glycolysis activity in CRC cells by elevating the ANGPTL4 expression in vitro and in vivo, which were necessary for the colonization of F. nucleatum itself. Furthermore, overall increased acetylation of histone H3 lysine 27 was observed in F. nucleatum infected CRC cells and clinical tumors, which was specifically responsible for the corresponding transcriptional regulation of ANGPTL4.Conclusion: This study suggests the metabolic reprogramming of CRC cells is essential for the persistence of F. nucleatum. By interfering ANGPTL4-mediated glycolysis enhancement of CRC cells, the F.nucleatum colonization and its tumor-promoting effects could be eradicated in CRC patients.

关键词： Fusobacterium nucleatum colorectal cancer glycolysis metabolic reprogramming histone acetylation ANGPTL4

Inhibition of NF-κB-dependent CX3CL1 upregulation attenuated the central sensitization and acute painful peripheral neuropathy following oxaliplatin treatment

在线全文

cnki会议

学校读者我要写书评

暂无评论

Inhibition of NF-κB-dependent CX3CL1 upregulation attenuate...

中国生理学会第24届全国会员代表大会暨生理学学术大会

作者：黄真真信文君李黛中山大学疼痛研究中心

Background:Acute and chronic painful peripheral neuropathy following the oxaliplatin treatment is the principle dose limiting factor for treatment discontinuation.Although it is generally accepted that axonopathy of peripheral nerves might mediated chronic painful peripheral neuropathy.However,It might be impossible that axonopathy of peripheral nerves can occur to contribute the acute peripheral neuropathy induced by oxaliplatin application.Results:ICP-MS analysis showed that the concentrations of oxaliplatin in cerebrospinal fluid（CSF）and plantar subcutaneous tissue showed a time-dependent increase following a single intraperitoneal administration of oxaliplatin（4 mg/kg）,which the dose induced the LTP of C-fiber-evoked field potentials and acute mechanical allodynia within 2 h.Furthermore,oxaliplatin at the detected dose（50n M,100μl）in the CSF by applied directly onto the spinal cord significantly induced the LTP of C-fiber-evoked field potentials and acute mechanical allodynia.However,intraplantar injection of oxaliplatin at detected dose（6ng/10μl）did not effect on the 50%withdrawal threshold and C-fiber-evoked field potentials compared with the vehicle group.In addition,application of oxaliplatin induced an upregulation of CX3CL1 expression,which is reduced significantly by NF-κB inhibitor PDTC or p65 si RNA.Blockade of either CX3CL1 or NF-κB signaling pathway prevented the LTP of C-fiber-evoked field potentials and acute mechanical allodynia induced by oxaliplatin drugs.The whole cell patch clamp results showed that blockade of CX3CL1 with neutralizing antibody attenuated the s EPSC and e EPSC increases induced by oxaliplatin in the projection NK1R neurons of lamina I.The further studies with chromatin immunoprecipitation（Ch IP）found that oxaliplatin increased the recruitment of NF-κB p65 to the Cx3cl1 promoter region.We also found an increased acetylation level of H4,but not H3,in Cx3cl1 promoter region following oxaliplatin treatment,which was reversed by inhibition of NF-κB with PDTC or p65 si RNA.Conclus

关键词： oxaliplatin CX3CL1 NF-κB LTP histone acetylation

Epigenetic modulation of Wnt signaling contributes to the neuropathic pain in the rats

在线全文

cnki会议

学校读者我要写书评

暂无评论

Epigenetic modulation of Wnt signaling contributes to the ne...

中国中西医结合麻醉学会[CSIA]年会暨第二届全国中西...

作者： Wei Feng Haichen Chu Ruynag Teng Yang Zhao Jie Gao Department of Anaesthiology Affiliated Hospital of Qingdao University

Emerging reports demonstrated that Wnt/β-catenin pathways critically contributed to the induction and maintenance of chronic pain induced by peripheral inflammation and nerve injury.Emerging evidences also suggested the critical role of epigenetic mechanism in the setting of chronic pain.The present study aims to elucidate the potential epigenetic mechanism underlying the altered Wnt signaling and its functional significance in the rats with neuropathic pain induced by chronic constriction injury(CCI) in sciatic nerve.In the present study significantly increased expression of Wnt3 a was observed in the dorsal horn of the rats with CCI.It was also found that significantly increased histone H3 acetylation and decreased cytosine methylation in the promoter region of Wntia in the dorsal horn of the rats with CCI.Intrathecal application of XAV939,an inhibitor of Wnt signaling,significantly decreased the expression of the active P-catenin and attenuated the painful behavioral response to thermal and mechanical stimuli in the rat with CCI.These results demonstrated an epigenetic upregulation of Wnt3 a in the dorsal horn,which critically contributed to the maintenance of painful behavior in the rats with neuropathic pain.

关键词： neuropathic pain Wnt histone acetylation cytosine methylation

长链非编码RNA H19和miR-200家族在肝癌转移过程中的关系和作用研究(英文)

在线全文

cnki会议

学校读者我要写书评

暂无评论

长链非编码RNA H19和miR-200家族在肝癌转移过程中的关系和作用研...

第十二次全国医学遗传学学术会议

作者：张铃杨富徐丹王芳孙树汉第二军医大学医学遗传学教研室

Background & Aims:Although numerous long non-coding RNAs(IncRNAs) have been identified in mammals,many of their biological roles remain to be characterized.Recently, long non-coding RNAs(LncRNAs) encoded in human genome have been shown to serve as important regulatory transcripts and may have other previously unappreciated functions.They can serve as scaffolds,aiding the association of proteins with genomic DNA.In our recent study,we identified nonoverlapping signatures of a small number of IncRNAs that are aberrantly expressed in human Hepatitis B virus(HBV)-related HCC compared with matched peritumoral tissues. Among these IncRNAs,H19 was found to play a potential role in HCC progression.Early reports suggest that H19 contributes to carcinogenesis,including hepatocellular carcinoma(HCC). Examination of the Oncomine resource showed that most HCC cases express H19 at a level that is comparable with the liver,with a tendency toward lower expression.This is consistent with our previous microarray data and indicates a more complicated role of H19 in HCC that needs to be characterized.Methods & Results:In this study,the expression level of H19 was assessed in different regions of HCC patients’liver samples.Notably,our results showed that the H19 RNA was enriched in the sections around the tumor tissues.This is in agreement with a previousreport that H19 was most prominent at the boundary of the tumor nodule.We collected tissues from different sites of the patients’livers,and we defined the peritumoral tissues as the sections that were 2 cm away from the tumor tissues and the normal tissues as the sections that were at least 3 cm away from the tumors.Loss- and gain-of-function studies on this IncRNA in the HCC cell lines,SMMC7721 and HCCLM3,were used to characterize its effects on gene expression and to assess its effect on HCC metastasis both in vitro and in vivo.In this study,we show that HI9 was underexpressed in intratumoral HCC tissues(T),as compared with peritumoral tissues(L). Additionally,low T/L ratio of H19

关键词： histone acetylation hepatocellular carcinoma peritumoral tissues epithelial-to-mesenchymal transition long non-coding RNA