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Histone deacetylases and cardiovascular cell lineage commitment

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World Journal of Stem Cells 2015年第5期7卷 852-859页

作者： Jun-Yao Yang Qian Wang Wen Wang Ling-Fang Zeng Laboratory Medicine Centre Nanfang Hospital Southern Medical University School of Engineering and Materials Science Queen Mary University of London Cardiovascular Division King’s College London

Cardiovascular diseases(CVDs), which include alldiseases of the heart and circulation system, are the leading cause of deaths on the globally. During the development of CVDs, choric inflammatory, lipid metabolism disorder and endothelial dysfunction are widely recognized risk factors. Recently, the new treatment for CVDs that designed to regenerate the damaged myocardium and injured vascular endothelium and improve recovery by the use of stem cells, attracts more and more public attention. Histone deacetylases(HDACs) are a family of enzymes that remove acetyl groups from lysine residues of histone proteins allowing the histones to wrap the DNA more tightly and commonly known as epigenetic regulators of gene transcription. HDACs play indispensable roles in nearly all biological processes, such as transcriptional regulation, cell cycle progression and developmental events, and have originally shown to be involved in cancer and neurological diseases. HDACs are also found to play crucial roles in cardiovascular diseases by modulating vascular cell homeostasis(e.g., proliferation, migration, and apoptosis of both ECs and SMCs). This review focuses on the roles of different members of HDACs and HDAC inhibitor on stem cell/ progenitor cell differentiation toward vascular cell lineages(endothelial cells, smooth muscle cells and Cardiomyocytes) and its potential therapeutics.

关键词： Histone deacetylases Stem cell Endothelialcell Smooth muscle cell Cardiovascular diseases

Histone deacetylases,microRNA and leptin crosstalk in pancreatic cancer

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World Journal of Clinical Oncology 2017年第3期8卷 178-189页

作者： Cynthia I Tchio Mantho Adriana Harbuzariu Ruben R Gonzalez-Perez Department of Microbiology Biochemistry and ImmunologyMorehouse School of Medicine

Because pancreatic cancer(PC) historically has had poor prognosis and five year survival rates,it has been intensely *** of PC incidence and biology has shown a link between different risk factors such as smoking,alcoholism,and obesity and disease *** factors affecting PC include the epigenomic changes driven by DNA methylation and histone acetylation,and actions of microRNA inducing oncogenic or tumor suppressor *** have identified markers whose dysregulation seem to play important roles in PC *** markers involve classical histone deacetylases(HDAC),PC stem cell(PCSC),and *** this review,we discuss the role of several PC biomarkers,and the potential crosstalk between HDAC,microRNA,and leptin in PC *** expression of these molecules can increase proliferation,survival,PCSC,resistance to chemotherapy and tumor *** potential relationships between these molecules are further analyzed using data from The Cancer Genome Atlas and crosstalk pathways generated by the Pathway Studio Platform(Ariadne Genomics,Inc.).Oncogenic miRNA21 and tumor suppressor miRNA200 have been previously linked to leptin *** analysis of PC biopsies and signaling crosstalk suggests that the main adipokine leptin could affect the expression of microRNA and HDAC in *** analysis suggests that HDAC-microRNA-leptin signaling crosstalk may be a new target for PC therapy.

关键词： Pancreatic Cancer MicroRNA Histone deacetylases Pancreatic cancer stem cell markers Leptin Obesity

HD2C Interacts with RPD3-type Histone deacetylases and is Involved in ABA and Salt Stress Response in Arabidopsis

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HD2C Interacts with RPD3-type Histone Deacetylases and is In...

Expression and subcellular localization of histone deacetylases in tomato(Solanum lycopersicum)

2010全国植物生物学研讨会

作者： Ming Luo Yu-Yuan Wang Yuhai Cui Keqiang Wu Southern Crop Protection and Food Research Centre Agriculture and Agri-Food Canada Institute of Plant Biology College of Life Science National Taiwan University South China Botanical Garden Chinese Academy of Sciences

HD2 proteins are plant specific histone *** HD2 proteins,HD2A,HD2B,HD2C and HD2D,have been identified in *** was found that the expression of HD2A,HD2B,HD2C and HD2D was repressed by ABA and Na *** further investigate... 详细信息

关键词： histone deacetylases HD2C HDA6 ABA Arabidopsis

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Expression and subcellular localization of histone deacetyla...

Tetrahydroisoquinolines as novel histone deacetylase inhibitors for treatment of cancer

2013全国植物生物学大会

作者： LU Jingxia YANG Songguang WU Keqiang South China Botanical Garden Chinese Academy of Sciences

Recent studies have indicated that the histone acetylation plays an important role in plant development and plant response to environmental *** tomato(Solanum lycopersicum),the respiratory

关键词： histone deacetylases tomato (Solanum lycopersicum) gene expression subcellular localization

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Acta Pharmaceutica Sinica B 2016年第1期6卷 93-99页

作者： Danqi Chen Aijun Shen Guanghua Fang Hongchun Liu Minmin Zhang Shuai Tang Bing Xiong Lanping Ma Meiyu Geng Jingkang Shen Department of Medicinal Chemistry State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of Science Division of Anti-tumor Pharmacology State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of Sciences

Histone acetylation is a critical process in the regulation of chromatin structure and gene *** deacetylases(HDACs)remove the acetyl group,leading to chromatin condensation and transcriptional *** inhibitors are considered a new class of anticancer agents and have been shown to alter gene transcription and exert antitumor *** paper describes our work on the structural determination and structure-activity relationship(SAR)optimization of tetrahydroisoquinoline compounds as HDAC *** compounds were tested for their ability to inhibit HDAC 1,3,6 and for their ability to inhibit the proliferation of a panel of cancer cell *** these,compound 82 showed the greatest inhibitory activity toward HDAC 1,3,6 and strongly inhibited growth of the cancer cell lines,with results clearly superior to those of the reference compound,vorinostat(SAHA).Compound 82 increased the acetylation of histones H3,H4 and tubulin in a concentration-dependent manner,suggesting that it is a broad inhibitor of HDACs.

关键词： Histone deacetylases inhibitor Anticancer Tetrahydroisoquinoline Structure–activity relationship

Alcohol-induced protein hyperacetylation: Mechanisms and consequences

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World Journal of Gastroenterology 2009年第10期15卷 1219-1230页

作者： Blythe D Shepard Pamela L Tuma Department of Biology The Catholic University of America 620 Michigan Avenue NE Washington DC 20064 United States

Although the clinical manifestations of alcoholic liver disease are well-described, little is known about the molecular basis of liver injury. Recent studies have indicated that ethanol exposure induces global protein hyperacetylationo This reversible, post- translational modification on the E-amino groups of lysine residues has been shown to modulate multiple, diverse cellular processes ranging from transcriptional activation to microtubule stability. Thus, alcohol- induced protein hyperacetylation likely leads to major physiological consequences that contribute to alcohol-induced hepatotoxicity. Lysine acetylation is controlled by the activities of two opposing enzymes, histone acetyltransferases and histone deacetylases. Currently, efforts are aimed at determining which enzymes are responsible for the increased acetylation of specific substrates. However, the greater challenge will be to determine the physiological ramifications of protein hyperacetylation and how they might contribute to the progression of liver disease. In this review, we will first list and discuss the proteins known to be hyperacetylated in the presence of ethanol. We will then describe what is known about the mechanisms leading to increased protein acetylation and how hyperacetylation may perturb hepatic function.

关键词： Ethanol Hepatotoxicity Acetylation deacetylases Acetyltransferases

Current evidence for histone deacetylase inhibitors in pancreatic cancer

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World Journal of Gastroenterology 2013年第6期19卷 813-828页

作者： Ioannis Koutsounas Constantinos Giaginis Efstratios Patsouris Stamatios Theocharis First Department of Pathology Medical SchoolNational and Kapodistrian University of AthensGR-11527 AthensGreece Department of Food Science and Nutrition University of the AegeanGR-81400 LemnosGreece

Pancreatic cancer is one of the most aggressive human cancers,with more than 200 000 deaths worldwide every *** recent efforts,conventional treatment approaches,such as surgery and classic chemotherapy,have only slightly improved patient *** effective and well-tolerated therapies are required to reverse the current poor prognosis of this type of *** new agents,histone deacetylase inhibitors (HDACIs) are now being *** have multiple biological effects related to acetylation of histones and many non-histone proteins that are involved in regulation of gene expression,apoptosis,cell cycle progression and *** induce cell cycle arrest and can activate the extrinsic and intrinsic pathways of apoptosis in different cancer cell *** the present review,the main mechanisms by which HDACIs act in pancreatic cancer cells in vitro,as well as their antiproliferative effects in animal models are *** constitute a promising treatment for pancreatic cancer with encouraging anti-tumor ef-fects,at well-tolerated doses.

关键词： Pancreatic cancer Histone deacetylases Histone deacetylase inhibitors Experimental studies

Histone deacetylase inhibitors and pancreatic cancer:Are there any promising clinical trials?

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World Journal of Gastroenterology 2013年第8期19卷 1173-1181页

作者： Ioannis Koutsounas Constantinos Giaginis Stamatios Theocharis Department of Forensic Medicine and Toxicology Medical SchoolUniversity of AthensGR-11527 AthensGreece Department of Food Science and Nutrition University of the AegeanGR-81400 LemnosGreece

Pancreatic cancer,although not very frequent,has an exceptionally high mortality rate,making it one of the most common causes of cancer mortality in developed *** cancer is difficult to diagnose,allowing few patients to have the necessary treatment at a relatively early *** a marginal benefit in survival,the overall response of pancreatic cancer to current systemic therapy continues to be poor,and new therapies are desperately *** deacetylase(HDAC) enzymes play an important role in the development and progression of cancer and HDAC inhibitors(HDACIs) have been shown to induce differentiation and cell cycle arrest,activate the extrinsic or intrinsic pathways of apoptosis,and inhibit invasion,migration and angiogenesis in different cancer cell *** a result of promising preclinical data,various HDACIs are being tested as either monotherapeutic agents or in combination regimens for both solid and hematological *** was the first HDACI approved by the Food and Drug Administration for patients with cutaneous T-cell *** use of HDACIs in clinical trials,in pretreated and relapsed patients suffering from advanced pancreatic cancer is ***,clinical data for HDACIs in patients with pancreatic cancer are inadequate,because only a few studies have included patients suffering from this type of neoplasm and the number of pancreatic cancer patients that entered HDACIs phase Ⅱ/Ⅲ trials,among others with advanced solid tumors,is very *** studies recruiting patients with pancreatic cancer remain to determine the efficiency of these therapies.

关键词： Pancreatic cancer Histone deacetylases Histone deacetylase inhibitors Clinical trials

DFT Study, Linear and Nonlinear Multiple Regression in the Prediction of HDAC7 Inhibitory Activities on a Series of Hydroxamic Acids

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Computational Molecular Bioscience 2019年第3期9卷 63-80页

作者： Doh Soro Lynda Ekou Bafétigué Ouattara Mamadou Guy-Richard Kone Tchirioua Ekou Nahossé Ziao Laboratoire de Thermodynamique et de Physico-Chimie du Milieu UFR SFA Université Nangui Abrogoua Abidjan C&#244 te-d’Ivoire Laboratoire de Physique Fondamentale et Appliquée Université Nangui Abrogoua C&#244 te d’Ivoire

In this work, we conducted a QSAR study on 18 molecules using descriptors from the Density Functional Theory (DFT) in order to predict the inhibitory activity of hydroxamic acids on histone deacetylase 7. This study is performed using the principal component analysis (PCA) method, the Ascendant Hierarchical Classification (AHC), the linear multiple regression method (LMR) and the nonlinear multiple regression (NLMR). DFT calculations were performed to obtain information on the structure and information on the properties on a series of hydroxamic acids compounds studied. Multivariate statistical analysis yielded two quantitative models (model MLR and model MNLR) with the quantum descriptors: electronic affinity (AE), vibration frequency of the OH bond (ν(OH)) and that of the NH bond (ν(NH)). The LMR model gives statistically significant results and shows a good predictability R2 = 0.9659, S = 0.488, F = 85 and p-value . Electronic affinity is the priority descriptor in predicting the activity of HDAC7 inhibitors in this study. The results obtained suggest that the descriptors derived from the DFT could be useful to predict the activity of histone deacetylase 7 inhibitors. These models were evaluated according to the criteria of Tropsha et al.

关键词： Hydroxamic Acids Histones deacetylases DFT Histones deacetylases Inhibitors QSAR