scholarly journals Dysregulation of Histone Acetyltransferases and Deacetylases in Cardiovascular Diseases

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Yonggang Wang ◽  
Xiao Miao ◽  
Yucheng Liu ◽  
Fengsheng Li ◽  
Quan Liu ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Treatment Options ◽  
Histone Acetyltransferases ◽  
Protein Acetylation ◽  
Cellular Processes ◽  
Disease States ◽  
Novel Approach ◽  
Artery Disease ◽  
New Evidence

Cardiovascular disease (CVD) remains a leading cause of mortality worldwide despite advances in its prevention and management. A comprehensive understanding of factors which contribute to CVD is required in order to develop more effective treatment options. Dysregulation of epigenetic posttranscriptional modifications of histones in chromatin is thought to be associated with the pathology of many disease models, including CVD. Histone acetyltransferases (HATs) and deacetylases (HDACs) are regulators of histone lysine acetylation. Recent studies have implicated a fundamental role of reversible protein acetylation in the regulation of CVDs such as hypertension, pulmonary hypertension, diabetic cardiomyopathy, coronary artery disease, arrhythmia, and heart failure. This reversible acetylation is governed by enzymes that HATs add or HDACs remove acetyl groups respectively. New evidence has revealed that histone acetylation regulators blunt cardiovascular and related disease states in certain cellular processes including myocyte hypertrophy, apoptosis, fibrosis, oxidative stress, and inflammation. The accumulating evidence of the detrimental role of histone acetylation in cardiac disease combined with the cardioprotective role of histone acetylation regulators suggests that the use of histone acetylation regulators may serve as a novel approach to treating the millions of patients afflicted by cardiac diseases worldwide.

scholarly journals lncRNA and Mechanisms of Drug Resistance in Cancers of the Genitourinary System

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2148 ◽  
Author(s):  
Dominik A. Barth ◽  
Jaroslav Juracek ◽  
Ondrej Slaby ◽  
Martin Pichler ◽  
George A. Calin
Keyword(s):  
Drug Resistance ◽  
Treatment Options ◽  
Cancer Therapies ◽  
Protein Coding ◽  
Genitourinary System ◽  
Cellular Processes ◽  
Rna Transcripts ◽  
Novel Therapeutic Strategies ◽  
Regulatory Functions

Available systemic treatment options for cancers of the genitourinary system have experienced great progress in the last decade. However, a large proportion of patients eventually develop resistance to treatment, resulting in disease progression and shorter overall survival. Biomarkers indicating the increasing resistance to cancer therapies are yet to enter clinical routine. Long non-coding RNAs (lncRNA) are non-protein coding RNA transcripts longer than 200 nucleotides that exert multiple types of regulatory functions of all known cellular processes. Increasing evidence supports the role of lncRNAs in cancer development and progression. Additionally, their involvement in the development of drug resistance across various cancer entities, including genitourinary malignancies, are starting to be discovered. Consequently, lncRNAs have been suggested as factors in novel therapeutic strategies to overcome drug resistance in cancer. In this review, the existing evidences on lncRNAs and their involvement in mechanisms of drug resistance in cancers of the genitourinary system, including renal cell carcinoma, bladder cancer, prostate cancer, and testicular cancer, will be highlighted and discussed to facilitate and encourage further research in this field. We summarize a significant number of lncRNAs with proposed pathways in drug resistance and available reported studies.

scholarly journals Active regulator of SIRT1 is required for cancer cell survival but not for SIRT1 activity

Open Biology ◽  
2013 ◽  
Vol 3 (11) ◽  
pp. 130130 ◽  
Author(s):  
John R. P. Knight ◽  
Simon J. Allison ◽  
Jo Milner
Keyword(s):  
Cell Survival ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Survival ◽  
Cancer Cell Lines ◽  
Cellular Processes ◽  
Disease States ◽  
Cancer Cell Survival ◽  
P53 Activation

The NAD + -dependent deacetylase SIRT1 is involved in diverse cellular processes, and has also been linked with multiple disease states. Among these, SIRT1 expression negatively correlates with cancer survival in both laboratory and clinical studies. Active regulator of SIRT1 (AROS) was the first reported post-transcriptional regulator of SIRT1 activity, enhancing SIRT1-mediated deacetylation and downregulation of the SIRT1 target p53. However, little is known regarding the role of AROS in regulation of SIRT1 during disease. Here, we report the cellular and molecular effects of RNAi-mediated AROS suppression, comparing this with the role of SIRT1 in a panel of human cell lines of both cancerous and non-cancerous origins. Unexpectedly, AROS is found to vary in its modulation of p53 acetylation according to cell context. AROS suppresses p53 acetylation only following the application of cell damaging stress, whereas SIRT1 suppresses p53 under all conditions analysed. This supplements the original characterization of AROS but indicates that SIRT1 activity can persist following suppression of AROS. We also demonstrate that knockdown of AROS induces apoptosis in three cancer cell lines, independent of p53 activation. Importantly, AROS is not required for the viability of three non-cancer cell lines indicating a putative role for AROS in specifically promoting cancer cell survival.

scholarly journals Histone Acetylation and Its Modifiers in the Pathogenesis of Diabetic Nephropathy

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Xiaoxia Li ◽  
Chaoyuan Li ◽  
Guangdong Sun
Keyword(s):  
Diabetic Nephropathy ◽  
Histone Acetylation ◽  
Histone Deacetylases ◽  
Vascular Complications ◽  
Therapeutic Approaches ◽  
Nonhistone Proteins ◽  
Amino Terminal ◽  
Cellular Processes ◽  
Diabetic Vascular Complications ◽  
New Evidence

Diabetic nephropathy (DN) remains a leading cause of mortality worldwide despite advances in its prevention and management. A comprehensive understanding of factors contributing to DN is required to develop more effective therapeutic options. It is becoming more evident that histone acetylation (HAc), as one of the epigenetic mechanisms, is thought to be associated with the etiology of diabetic vascular complications such as diabetic retinopathy (DR), diabetic cardiomyopathy (DCM), and DN. Histone acetylases (HATs) and histone deacetylases (HDACs) are the well-known regulators of reversible acetylation in the amino-terminal domains of histone and nonhistone proteins. In DN, however, the roles of histone acetylation (HAc) and these enzymes are still controversial. Some new evidence has revealed that HATs and HDACs inhibitors are renoprotective in cellular and animal models of DN, while, on the other hand, upregulation of HAc has been implicated in the pathogenesis of DN. In this review, we focus on the recent advances on the roles of HAc and their covalent enzymes in the development and progression of DN in certain cellular processes including fibrosis, inflammation, hypertrophy, and oxidative stress and discuss how targeting these enzymes and their inhibitors can ultimately lead to the therapeutic approaches for treating DN.

scholarly journals A Role for Gcn5-Mediated Global Histone Acetylation in Transcriptional Regulation

2006 ◽  
Vol 26 (5) ◽  
pp. 1610-1616 ◽  
Author(s):  
Rachel Maria Imoberdorf ◽  
Irini Topalidou ◽  
Michel Strubin
Keyword(s):  
Histone Acetylation ◽  
Core Promoter ◽  
Histone Acetyltransferases ◽  
Gene Promoters ◽  
Core Promoters ◽  
The Core ◽  
Strength Of Interaction ◽  
Genome Wide ◽  
The Common

ABSTRACT Transcriptional activators often require histone acetyltransferases (HATs) for full activity. The common explanation is that activators directly recruit HATs to gene promoters to locally hyperacetylate histones and thereby facilitate transcription complex formation. However, in addition to being targeted to specific loci, HATs such as Gcn5 also modify histones genome-wide. Here we provide evidence for a role of this global HAT activity in regulated transcription. We show that activation by direct recruitment of the transcriptional machinery neither recruits Gcn5 nor induces changes in histone acetylation yet can strongly depend on Gcn5 at promoters showing a high basal state of Gcn5-mediated histone acetylation. We also show that Gcn5 dependency varies among core promoters and is influenced by the strength of interaction used to recruit the machinery and by the affinity of the latter for the core promoter. These data support a role for global Gcn5 HAT activity in modulating transcription independently of its known coactivator function.

Hypertension

2021 ◽  
pp. 43-61
Keyword(s):  
Renal Disease ◽  
Renal Artery ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Western World ◽  
Interventional Treatment ◽  
Lifestyle Modifications ◽  
Artery Disease ◽  
Progressive Renal Disease

Hypertension (HTN) is a common condition and a risk factor for numerous comorbidities, including cardiovascular disease, cerebrovascular disease, and progressive renal disease. In many people the aetiology of HTN is unknown, but in some a triggering “secondary” cause can be identified, e.g. renal disease, endocrine, or other underlying condition. For most people the treatment of HTN is straightforward, but in a small number the blood pressure can become “malignant or accelerated” and require urgent treatment or hospitalization. The chapters in this section provide an overview of the clinical assessment and investigation of a hypertensive patient, the recommended lifestyle modifications and pharmacological treatment options available, and potential complications of HTN. Renal artery stenosis a common cause of HTN that can be caused by atheromatous renovascular disease (ARVD) or other rarer pathologies, including fibromuscular disease, Takayasu’s arteritis, or other syndromes. ARVD is the commonest cause of renal artery disease in the Western world and in this section the authors focus upon the epidemiology and clinical presentation of ARVD and the potential diagnostic and treatment strategies. A particular focus is given to the role of medical and interventional treatment of ARVD, including potential outcomes, complications, and prognosis.

An update on the management of gout

2018 ◽  
Vol 56 (1) ◽  
pp. 9-12 ◽  
Keyword(s):  
Treatment Options ◽  
New Drugs ◽  
British Society ◽  
European League Against Rheumatism ◽  
Urate Lowering Treatment ◽  
The Uk ◽  
New Evidence ◽  
Urate Crystals

Gout is the most common form of inflammatory arthritis and its incidence in the UK has steadily increased from 1.5% in 1997 to 2.5% in 2012.1,2 It is characterised by deposition of monosodium urate crystals in joints and tissues and usually presents with intermittent painful attacks followed by long periods of remission.3 It has been suggested that the management of gout in the UK remains suboptimal.1 In 2004, we concluded that there was a woeful lack of evidence to guide treatment or prophylaxis for gout, particularly with regard to choice of drug or doses.4 The introduction of new drugs and new evidence on the efficacy and safety of treatment options has led the European League Against Rheumatism (EULAR) and the British Society of Rheumatology (BSR) to update their guidelines on the management of gout.2,5 Nevertheless, there are differing views on target serum uric acid (SUA) levels and the role of urate lowering treatment (ULT).2,5–7 Here, we review the latest guidance on the management of gout and consider the role of long-term ULT.

scholarly journals A STUDY OF THE ROLE OF MICRORNA IN PITUITARY ADENOMA

2018 ◽  
Vol 5 (2) ◽  
pp. 8-15
Author(s):  
I. F. Gareev ◽  
O. A. Beylerli
Keyword(s):  
Pituitary Adenoma ◽  
Target Genes ◽  
Decisive Role ◽  
Cellular Processes ◽  
New Class ◽  
Number Of Genes ◽  
Non Coding Rnas ◽  
New Biomarkers ◽  
New Evidence

MicroRNAs are a new class of small non-coding RNAs, a length of 18–22 nucleotides that play a decisive role as posttranscriptional regulators of gene expression. Due to the large number of genes, regulated microRNAs, microRNAs are involved in many cellular processes. The study of the impairment of the expression of the target genes of microRNA, often associated with changes in important biological characteristics, provides a significant understanding of the role of microRNAs in oncogenesis. New evidence suggests that aberrant microRNA expression or dysregulation of endogenous microRNAs affects the onset and development of tumors, including adenomas of the pituitary gland. In this review, the significance of some microRNAs in the pathology of the pituitary adenoma will be assessed, as well as data on the study of microRNAs as therapeutic targets and new biomarkers.

Platelets and Cardiovascular Disease

2002 ◽  
Vol 1 (4) ◽  
pp. 273-288 ◽  
Author(s):  
Scott Willoughby ◽  
Andrew Holmes ◽  
Joseph Loscalzo
Keyword(s):  
Cardiovascular Disease ◽  
Stable Angina Pectoris ◽  
Platelet Dysfunction ◽  
Normal Response ◽  
Comprehensive Overview ◽  
Disease States ◽  
Artery Disease ◽  
Platelet Hyperaggregability ◽  
Physiologic Role

Platelets play an important, but often under-recognized role in cardiovascular disease. For example, the normal response of the platelet can be altered, either by increased pro-aggregatory stimuli or by diminished anti-aggregatory substances to produce conditions of increased platelet activation/aggregation and occur in active cardiovascular disease states both on a chronic (e.g. stable angina pectoris) and acute basis (e.g. acute myocardial infarction). In addition, platelet hyperaggregability is also associated with the risk factors for coronary artery disease (e.g. smoking, hypertension, and hypercholesterolaemia). Finally, the utility of an increasing range of anti-platelet therapies in the management of the above disease states further emphasizes the pivotal role platelets play in the pathogenesis of cardiovascular disease. This paper provides a comprehensive overview of the normal physiologic role of platelets in maintain homeostasis, the pathophysiologic processes that contribute to platelet dysfunction in cardiovascular disease and the associated role and benefits of anti-platelet therapies.

scholarly journals Protein Acetylation Induced by Dichloroacetate (DCA) Treatment is Associated with Decreased Respiration in Cultured Hepatocytes: Preliminary Results

2019 ◽  
Author(s):  
Jesse G. Meyer
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Physiological Role ◽  
Pyruvate Dehydrogenase Kinase ◽  
Protein Acetylation ◽  
Post Translational Modification ◽  
Cellular Processes ◽  
Excess Production ◽  
Lysine Residues ◽  
Genetic Perturbations

AbstractProtein post-translational modification (PTM) by acetylation at the ε-amine on lysine residues in proteins regulates various cellular processes including transcription and metabolism. Several metabolic and genetic perturbations are known to increase acetylation of various proteins. Hyper-acetylation can also be induced using deacetylase inhibitors. While there is much interest in discovering drugs that can reverse protein acetylation, pharmacological tools that increase non-enzymatic protein acetylation are needed in order to understand the physiological role of excess protein acetylation. In this study, I assessed whether inhibition of pyruvate dehydrogenase kinase (PDHK) could cause protein hyper-acetylation due to excess production of acetyl-CoA by pyruvate dehydrogenase (PDH). Western blot of total protein from dichloroacetate (DCA) treated hepatocytes with anti-acetyl-lysine antibody showed increased protein acetylation, and seahorse respirometry of DCA pretreated hepatocytes indicated a subtle decrease in basal and maximal respiratory capacity.

scholarly journals Targeting GPCRs & their Signaling as a Therapeutic Option in Melanoma

2022 ◽  
Author(s):  
Jeremy H Raymond ◽  
Zackie Aktary ◽  
Lionel Larue ◽  
Véronique Delmas
Keyword(s):  
Therapeutic Option ◽  
Treatment Options ◽  
Paracrine Factors ◽  
Downstream Signaling ◽  
Cellular Processes ◽  
Activating Mutations ◽  
New Therapeutic Approaches ◽  
And Migration ◽  
G Protein Coupled

G protein-coupled receptors (GPCRs) serve prominent roles in melanocyte lineage physiology, with an impact at all stages of development, as well as on mature melanocyte functions. GPCR ligands are present in the skin and regulate melanocyte homeostasis, including pigmentation. The role of GPCRs in the regulation of pigmentation and, consequently, protection against external aggression, such as ultraviolet radiation, has long been established. However, evidence of new functions of GPCRs directly in melanomagenesis has been highlighted in recent years. GPCRs are coupled, through their intracellular domains, to heterotrimeric G proteins, which induce cellular signaling through various pathways. Such signaling modulates essential cellular processes of melanomagenesis, such as proliferation and migration. GPCR-associated signaling in melanoma can be activated by the binding of paracrine factors to their receptors or directly by activating mutations. In this review, we present melanoma-associated alterations of GPCRs and their downstream signaling and discuss the various preclinical models used to evaluate new therapeutic approaches against GPCR activity in melanoma. Recent striking advances in our understanding of the structure, function, and regulation of GPCRs will undoubtedly broaden treatment options in melanoma in the future.

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