scholarly journals The role of sirtuins in cardiac disease

2015 ◽  
Vol 309 (9) ◽  
pp. H1375-H1389 ◽  
Author(s):  
Shouji Matsushima ◽  
Junichi Sadoshima
Keyword(s):  
Cardiac Hypertrophy ◽  
Mating Type ◽  
Stress Responses ◽  
Histone Deacetylases ◽  
Class Iii ◽  
Beneficial Effects ◽  
Damage Repair ◽  
Wide Range ◽  
Apoptosis And Inflammation

Modification of histones is one of the important mechanisms of epigenetics, in which genetic control is determined by factors other than an individual's DNA sequence. Sirtuin family proteins, which are class III histone deacetylases, were originally identified as gene silencers that affect the mating type of yeast, leading to the name “silent mating-type information regulation 2” (SIR2). They are characterized by their requirement of nicotinamide adenine dinucleotide for their enzyme activity, unlike other classes of histone deacetylases. Sirtuins have been traditionally linked to longevity and the beneficial effects of calorie restriction and DNA damage repair. Recently, sirtuins have been shown to be involved in a wide range of physiological and pathological processes, including aging, energy responses to low calorie availability, and stress resistance, as well as apoptosis and inflammation. Sirtuins can also regulate mitochondrial biogenesis and circadian clocks. Seven sirtuin family proteins (Sirt1-7) have been identified as mammalian SIR2 orthologs, localized in different subcellular compartments, namely, the cytoplasm (Sirt1, 2), the mitochondria (Sirt3, 4, 5), and the nucleus (Sirt1, 2, 6, 7). Sirt1 is evolutionarily close to yeast SIR2 and has been the most intensively investigated in the cardiovascular system. Endogenous Sirt1 plays a pivotal role in mediating the cell death/survival process and has been implicated in the pathogenesis of cardiovascular disease. Downregulation of Sirt2 is protective against ischemic-reperfusion injury. Increased Sirt3 expression has been shown to correlate with longevity in humans. In addition, Sirt3 protects cardiomyocytes from aging and oxidative stress and suppresses cardiac hypertrophy. Sirt6 has also recently been demonstrated to attenuate cardiac hypertrophy, and Sirt7 is known to regulate apoptosis and stress responses in the heart. On the other hand, the roles of Sirt4 and Sirt5 in the heart remain largely uncharacterized.

scholarly journals The Role of Sirtuins in Kidney Diseases

2020 ◽  
Vol 21 (18) ◽  
pp. 6686
Author(s):  
Yu Ah Hong ◽  
Ji Eun Kim ◽  
Minjee Jo ◽  
Gang-Jee Ko
Keyword(s):  
Histone Deacetylases ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Kidney Diseases ◽  
Expression Profiles ◽  
Kidney Injury ◽  
Class Iii ◽  
Cellular Functions ◽  
Wide Range

Sirtuins (SIRTs) are class III histone deacetylases (HDACs) that play important roles in aging and a wide range of cellular functions. Sirtuins are crucial to numerous biological processes, including proliferation, DNA repair, mitochondrial energy homeostasis, and antioxidant activity. Mammals have seven different sirtuins, SIRT1–7, and the diverse biological functions of each sirtuin are due to differences in subcellular localization, expression profiles, and cellular substrates. In this review, we summarize research advances into the role of sirtuins in the pathogenesis of various kidney diseases including acute kidney injury, diabetic kidney disease, renal fibrosis, and kidney aging along with the possible underlying molecular mechanisms. The available evidence indicates that sirtuins have great potential as novel therapeutic targets for the prevention and treatment of kidney diseases.

The Protective Mechanism of SIRT1 in the Regulation of Mitochondrial Biogenesis and Mitochondrial Autophagy in Alzheimer’s Disease

2021 ◽  
pp. 1-9
Author(s):  
Fan Ye ◽  
Anshi Wu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Biogenesis ◽  
Stress Responses ◽  
Histone Deacetylases ◽  
Neuronal Morphology ◽  
Protective Mechanism ◽  
Peroxisome Proliferator ◽  
Class Iii ◽  
Peroxisome Proliferator Activated Receptor

Silent information-regulated transcription factor 1 (SIRT1) is the most prominent and widely studied member of the sirtuins (a family of mammalian class III histone deacetylases). It is a nuclear protein, and the deacetylation of the peroxisome proliferator-activated receptor coactivator-1 has been extensively implicated in metabolic control and mitochondrial biogenesis and is the basis for studies into its involvement in caloric restriction and its effects on lifespan. The present study discusses the potentially protective mechanism of SIRT1 in the regulation of the mitochondrial biogenesis and autophagy involved in the modulation of Alzheimer’s disease, which may be correlated with the role of SIRT1 in affecting neuronal morphology, learning, and memory during development; regulating metabolism; counteracting stress responses; and maintaining genomic stability. Drugs that activate SIRT1 may offer a promising approach to treating Alzheimer’s disease

Omentin-1 attenuates glucocorticoid-induced cardiac injury by phosphorylating GSK3β

2021 ◽  
Vol 66 (4) ◽  
pp. 273-283
Author(s):  
Zhousheng Jin ◽  
Fangfang Xia ◽  
Jiaojiao Dong ◽  
Tingting Lin ◽  
Yaoyao Cai ◽  
...  
Keyword(s):  
Side Effects ◽  
Cardiac Hypertrophy ◽  
Cardiac Injury ◽  
Experimental Studies ◽  
Chronic Administration ◽  
Cardiovascular Complications ◽  
Rat Serum ◽  
Cardiac Side Effects ◽  
Beneficial Effects

Glucocorticoid excess often causes a variety of cardiovascular complications, including hypertension, atherosclerosis, and cardiac hypertrophy. To abrogate its cardiac side effects, it is necessary to fully disclose the pathophysiological role of glucocorticoid in cardiac remodelling. Previous clinical and experimental studies have found that omentin-1, one of the adipokines, has beneficial effects in cardiovascular diseases, and is closely associated with metabolic disorders. However, there is no evidence to address the potential role of omentin-1 in glucocorticoid excess-induced cardiac injuries. To uncover the links, the present study utilized rat model with glucocorticoid-induced cardiac injuries and clinical patients with abnormal cardiac function. Chronic administration of glucocorticoid excess reduced rat serum omentin-1 concentration, which closely correlated with cardiac functional parameters. Intravenous administration of adeno-associated virus encoding omentin-1 upregulated the circulating omentin-1 level and attenuated glucocorticoid excess-induced cardiac hypertrophy and functional disorders. Overexpression of omentin-1 also improved cardiac mitochondrial function, including the reduction of lipid deposits, induction of mitochondrial biogenesis, and enhanced mitochondrial activities. Mechanistically, omentin-1 phosphorylated and activated the GSK3β pathway in the heart. From a study of 28 patients with Cushing’s syndrome and 23 healthy subjects, the plasma level of glucocorticoid was negatively correlated with omentin-1, and was positively associated with cardiac ejection fraction and fractional shortening. Collectively, the present study provided a novel role of omentin-1 in glucocorticoid excess-induced cardiac injuries and found that the omentin-1/GSK3β pathway was a potential therapeutic target in combating the side effects of glucocorticoid.

Resveratrol

2017 ◽  
pp. 288-308 ◽  
Author(s):  
Catherine A. Powell ◽  
Jian Zhang ◽  
John D. Bowman ◽  
Mahua Choudhury
Keyword(s):  
Histone Deacetylases ◽  
Target Genes ◽  
Therapeutic Option ◽  
Genetic Regulation ◽  
The Body ◽  
Class Iii ◽  
Beneficial Effects ◽  
Epigenetic Regulator ◽  
Cardioprotective Effects ◽  
Genetic Makeup

Cardiovascular disease (CVD) is the leading cause of death in both men and women and has largely been attributed to genetic makeup and lifestyle factors. However, genetic regulation does not fully explain the pathophysiology. Recently, epigenetic regulation, the regulation of the genetic code by modifications that affect the transcription and translation of target genes, has been shown to be important. Silent information regulator-2 proteins or sirtuins are an epigenetic regulator family of class III histone deacetylases (HDACs), unique in their dependency on coenzyme NAD+, that are postulated to mediate the beneficial effects of calorie restriction, thus promoting longevity by reducing the incidence of chronic diseases such as cancer, diabetes, and CVD. Emerging evidence shows that SIRT1 is ubiquitously expressed throughout the body. Resveratrol, a plant polyphenol, has cardioprotective effects and its mechanism of action is attributed to regulation of SIRT1. Incoproation of resveratrol into the diet may be a powerful therapeutic option for the prevention and treatment of CVD.

scholarly journals N-Acetylglucosamine Regulates Morphogenesis and Virulence Pathways in Fungi

2019 ◽  
Vol 6 (1) ◽  
pp. 8 ◽  
Author(s):  
Kyunghun Min ◽  
Shamoon Naseem ◽  
James B. Konopka
Keyword(s):  
Cell Wall ◽  
Stress Responses ◽  
Hyphal Growth ◽  
Amino Sugar ◽  
Model Organisms ◽  
Animal Cells ◽  
Epigenetic Switch ◽  
Wide Range ◽  
Extracellular Environment

N-acetylglucosamine (GlcNAc) is being increasingly recognized for its ability to stimulate cell signaling. This amino sugar is best known as a component of cell wall peptidoglycan in bacteria, cell wall chitin in fungi and parasites, exoskeletons of arthropods, and the extracellular matrix of animal cells. In addition to these structural roles, GlcNAc is now known to stimulate morphological and stress responses in a wide range of organisms. In fungi, the model organisms Saccharomyces cerevisiae and Schizosaccharomyces pombe lack the ability to respond to GlcNAc or catabolize it, so studies with the human pathogen Candida albicans have been providing new insights into the ability of GlcNAc to stimulate cellular responses. GlcNAc potently induces C. albicans to transition from budding to filamentous hyphal growth. It also promotes an epigenetic switch from White to Opaque cells, which differ in morphology, metabolism, and virulence properties. These studies have led to new discoveries, such as the identification of the first eukaryotic GlcNAc transporter. Other results have shown that GlcNAc can induce signaling in C. albicans in two ways. One is to act as a signaling molecule independent of its catabolism, and the other is that its catabolism can cause the alkalinization of the extracellular environment, which provides an additional stimulus to form hyphae. GlcNAc also induces the expression of virulence genes in the C. albicans, indicating it can influence pathogenesis. Therefore, this review will describe the recent advances in understanding the role of GlcNAc signaling pathways in regulating C. albicans morphogenesis and virulence.

scholarly journals SIRT7-mediated ATM deacetylation is essential for its deactivation and DNA damage repair

2019 ◽  
Vol 5 (3) ◽  
pp. eaav1118 ◽  
Author(s):  
Ming Tang ◽  
Zhiming Li ◽  
Chaohua Zhang ◽  
Xiaopeng Lu ◽  
Bo Tu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Repair ◽  
Class Iii ◽  
Ataxia Telangiectasia Mutated ◽  
Damage Repair ◽  
Damage Response ◽  
Late Stages

The activation of ataxia-telangiectasia mutated (ATM) upon DNA damage involves a cascade of reactions, including acetylation by TIP60 and autophosphorylation. However, how ATM is progressively deactivated after completing DNA damage repair remains obscure. Here, we report that sirtuin 7 (SIRT7)–mediated deacetylation is essential for dephosphorylation and deactivation of ATM. We show that SIRT7, a class III histone deacetylase, interacts with and deacetylates ATM in vitro and in vivo. In response to DNA damage, SIRT7 is mobilized onto chromatin and deacetylates ATM during the late stages of DNA damage response, when ATM is being gradually deactivated. Deacetylation of ATM by SIRT7 is prerequisite for its dephosphorylation by its phosphatase WIP1. Consequently, depletion of SIRT7 or acetylation-mimic mutation of ATM induces persistent ATM phosphorylation and activation, thus leading to impaired DNA damage repair. Together, our findings reveal a previously unidentified role of SIRT7 in regulating ATM activity and DNA damage repair.

scholarly journals Endothelial Spns2 and ApoM Regulation of Vascular Tone and Hypertension Via Sphingosine‐1‐Phosphate

2021 ◽  
Author(s):  
Ilaria Del Gaudio ◽  
Luisa Rubinelli ◽  
Linda Sasset ◽  
Christian Wadsack ◽  
Timothy Hla ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Vascular Tone ◽  
Density Lipoprotein ◽  
No Production ◽  
Beneficial Effects ◽  
Increased Risk ◽  
Sphingosine 1 Phosphate

Background Most of the circulating sphingosine‐1‐phosphate (S1P) is bound to ApoM (apolipoprotein M) of high‐density lipoprotein (HDL) and mediates many beneficial effects of HDL on the vasculature via G protein–coupled S1P receptors. HDL‐bound S1P is decreased in atherosclerosis, myocardial infarction, and diabetes mellitus. In addition to being the target, the endothelium is a source of S1P, which is transported outside of the cells by Spinster‐2, contributing to circulating S1P as well as to local signaling. Mice lacking endothelial S1P receptor 1 are hypertensive, suggesting a vasculoprotective role of S1P signaling. This study investigates the role of endothelial‐derived S1P and ApoM‐bound S1P in regulating vascular tone and blood pressure. Methods and Results ApoM knockout (ApoM KO) mice and mice lacking endothelial Spinster‐2 (ECKO‐Spns2) were infused with angiotensin II for 28 days. Blood pressure, measured by telemetry and tail‐cuff, was significantly increased in both ECKO‐Spns2 and ApoM KO versus control mice, at baseline and following angiotensin II. Notably, ECKO‐Spns2 presented an impaired vasodilation to flow and blood pressure dipping, which is clinically associated with increased risk for cardiovascular events. In hypertension, both groups presented reduced flow‐mediated vasodilation and some degree of impairment in endothelial NO production, which was more evident in ECKO‐Spns2. Increased hypertension in ECKO‐Spns2 and ApoM KO mice correlated with worsened cardiac hypertrophy versus controls. Conclusions Our study identifies an important role for Spinster‐2 and ApoM‐HDL in blood pressure homeostasis via S1P‐NO signaling and dissects the pathophysiological impact of endothelial‐derived S1P and ApoM of HDL‐bound S1P in hypertension and cardiac hypertrophy.

scholarly journals Zika virus infection drives epigenetic modulation of immunity by the histone acetyltransferase CBP of Aedes aegypti

2021 ◽  
Author(s):  
Anderson de Mendonca Amarante ◽  
Isabel Caetano de Abreu da Silva ◽  
Amanda Roberta Revoredo Vicentino ◽  
Vitor Coutinho Carneiro ◽  
Marcia de Amorim Pinto ◽  
...  
Keyword(s):  
Virus Infection ◽  
Aedes Aegypti ◽  
Zika Virus ◽  
Histone Deacetylases ◽  
Histone Acetyltransferase ◽  
Fat Body ◽  
Survival Rates ◽  
Immune Genes ◽  
Wide Range

Epigenetic mechanisms are responsible for a wide range of biological phenomena in insects, controlling embryonic development, growth, aging and nutrition. Despite this, the role of epigenetics in shaping insect-pathogen interactions has received little attention. Gene expression in eukaryotes is regulated by histone acetylation/deacetylation, an epigenetic process mediated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this study, we explored the role of the Aedes aegypti histone acetyltransferase CBP (AaCBP) after infection with Zika virus, focusing on the two main immune tissues, the midgut and fat body. We showed that the expression and activity of AaCBP could be positively modulated by blood meal and Zika infection. Nevertheless, Zika-infected mosquitoes that were silenced for AaCBP revealed a significant reduction in the acetylation of H3K27 (CBP target-marker), followed by downmodulation of the expression of immune genes, higher titers of Zika virus and lower survival rates. Importantly, in Zika-infected mosquitoes that were treated with sodium butyrate, a histone deacetylase inhibitor, their capacity to fight virus infection was rescued. Our data point to a direct correlation among histone hyperacetylation by AaCBP, upregulation of antimicrobial peptide genes and increased survival of Zika-infected-A. aegypti.

scholarly journals Stress and ageing in yeast

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Ian W Dawes ◽  
Gabriel G Perrone
Keyword(s):  
Yeast Cell ◽  
Cross Talk ◽  
Stress Responses ◽  
Cellular Responses ◽  
Ageing Process ◽  
Negative Effects ◽  
Beneficial Effects ◽  
Cellular Processes ◽  
Early Stress

ABSTRACT There has long been speculation about the role of various stresses in ageing. Some stresses have beneficial effects on ageing—dependent on duration and severity of the stress, others have negative effects and the question arises whether these negative effects are causative of ageing or the result of the ageing process. Cellular responses to many stresses are highly coordinated in a concerted way and hence there is a great deal of cross-talk between different stresses. Here the relevant aspects of the coordination of stress responses and the roles of different stresses on yeast cell ageing are discussed, together with the various functions that are involved. The cellular processes that are involved in alleviating the effects of stress on ageing are considered, together with the possible role of early stress events on subsequent ageing of cells.

scholarly journals Regulation of Chemokines and Cytokines by Histone Deacetylases and an Update on Histone Decetylase Inhibitors in Human Diseases

2019 ◽  
Vol 20 (5) ◽  
pp. 1110 ◽  
Author(s):  
Himavanth Gatla ◽  
Nethaji Muniraj ◽  
Prashanth Thevkar ◽  
Siddhartha Yavvari ◽  
Sahithi Sukhavasi ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
Viral Infections ◽  
Kidney Diseases ◽  
Hdac Inhibitors ◽  
Cardiovascular Complications ◽  
Human Diseases ◽  
Wide Range ◽  
Hematological Cancers ◽  
Anti Tumor Activity

Histone acetyltransferases (HATs) and histone deacetylases (HDACs) counteract with each other to regulate gene expression by altering chromatin structure. Aberrant HDAC activity was reported in many human diseases including wide range of cancers, viral infections, cardiovascular complications, auto-immune diseases and kidney diseases. HDAC inhibitors are small molecules designed to block the malignant activity of HDACs. Chemokines and cytokines control inflammation, immunological and other key biological processes and are shown to be involved in various malignancies. Various HDACs and HDAC inhibitors were reported to regulate chemokines and cytokines. Even though HDAC inhibitors have remarkable anti-tumor activity in hematological cancers, they are not effective in treating many diseases and many patients relapse after treatment. However, the role of HDACs and cytokines in regulating these diseases still remain unclear. Therefore, understanding exact mechanisms and effector functions of HDACs are urgently needed to selectively inhibit them and to establish better a platform to combat various malignancies. In this review, we address regulation of chemokines and cytokines by HDACs and HDAC inhibitors and update on HDAC inhibitors in human diseases.

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