scholarly journals SIRT1 and Kidney Function

2015 ◽  
Vol 1 (4) ◽  
pp. 258-265 ◽  
Author(s):  
Yi Guan ◽  
Chuan-Ming Hao
Keyword(s):  
Histone Deacetylases ◽  
Acute Stress ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Renal Medulla ◽  
Cyst Formation ◽  
Renal Physiology ◽  
Dna Integrity ◽  
Class Iii ◽  
Nonhistone Proteins

Background: SIRT1 is a nicotinamide adenine dinucleotide-dependent deacetylase belonging to the class III histone deacetylases. Abundantly expressed in the kidney, especially in the renal medulla, SIRT1 is closely involved in renal physiology and pathology. Summary: SIRT1 targets both histone and nonhistone proteins, participates in many important signaling pathways and mediates the regulation of longevity, metabolic homeostasis, acute stress response and DNA integrity. With regard to the kidney, SIRT1 attenuates diabetic albuminuria, reduces blood pressure and related cardiovascular diseases, resists acute kidney injury, delays kidney fibrogenesis, promotes cyst formation and benefits renal ageing. Key Messages: This review summarizes the biology of SIRT1 and focuses on the latest studies concerning SIRT1 as a potential therapeutic target for kidney diseases.

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.

scholarly journals MO1031FROM MARCELLO MALPIGHI  THROUGH  JEAN REDMAN OLIVER AND JOSEP TRUETA: A CONTINUING CONTRIBUTION TO THE “BLACK BOX”  CLINICAL PREDICTION MODELS IN NEPHROLOGY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Enrico Favaro ◽  
Roberta Lazzarin ◽  
Daniela Cremasco ◽  
Erika Pierobon ◽  
Marta Guizzo ◽  
...  
Keyword(s):  
Machine Learning ◽  
Acute Kidney Injury ◽  
Prediction Models ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Black Box ◽  
Renal Physiology ◽  
Clinical Prediction ◽  
Renal Circulation ◽  
Clinical Prediction Models

Abstract Background and Aims The modern development of the black box approach in clinical nephrology is inconceivable without a logical theory of renal function and a comprehension of anatomical architecture of the kidney, in health and disease: this is the undisputed contribution offered by Malpighi, Oliver and Trueta starting from the seventeenth century. The machine learning model for the prediction of acute kidney injury, progression of renal failure and tubulointerstitial nephritis is a good example of how different knowledge about kidney are an indispensable tool for the interpretation of model itself. Method Historical data were collected from literature, textbooks, encyclopedias, scientific periodicals and laboratory experimental data concerning these three authors. Results The Italian Marcello Malpighi (1628-1694), born in Crevalcore near Bologna, was Professor of anatomy at Bologna, Pisa and Messina. The historic description of the pulmonary capillaries was made in his second epistle to Borelli published in 1661 and intitled De pulmonibus, by means of the frog as “the microscope of nature” (Fig. 1). It is the first description of capillaries in any circulation. William Harvey in De motu cordis in 1628 (year of publication the same of date of birth of Italian anatomist!) could not see the capillary vessels. This thriumphant discovery will serve for the next reconnaissance of characteristic renal rete mirabile.in the corpuscle of Malpighi, lying within the capsule of Bowman. Jean Redman Oliver (1889-1976), a pathologist born and raised in Northern California, was able to bridge the gap between the nephron and collecting system through meticulous dissections, hand drawn illustrations and experiments which underpin our current understanding of renal anatomy and physiology. In the skillful lecture “When is the kidney not a kidney?” (1949) Oliver summarizes his far-sighted vision on renal physiology and disease in the following sentence: the Kidney in health, if you will, but the Nephrons in disease. Because, the “nephron” like the “kidney” is an abstraction that must be qualified in terms of its various parts, its cellular components and the molecular mechanisms involved in each discrete activity (Fig. 2). The Catalan surgeon Josep Trueta I Raspall (1897-1977) was born in the Poblenou neighborhood of Barcelona. His impact of pioneering and visionary contribution to the changes in renal circulation for the pathogenesis of acute kidney injury was pivotal for history of renal physiology. “The kidney has two potential circulatory circulations. Blood may pass either almost exclusively through one or other of two pathways, or to a varying degree through both”. (Studies of the Renal Circulation, published in 1947). Now this diversion of blood from cortex to the less resistant medullary circulation is known with the eponym Trueta shunt. Conclusion The black box approach to the kidney diseases should be considered by practitioners as a further tool to help to inform model update in many clinical setting. The number of machine learning clinical prediction models being published is rising, as new fields of application are being explored in medicine (Fig. 3). A challenge in the clinical nephrology is to explore the “kidney machine” during each therapeutic diagnostic procedure. Always, the intriguing relationship between the set of nephrological syndromes and kidney diseases cannot disregard the precious notions the specific organization of kidney microcirculation, fruit of many scientific contributions of the work by Malpighi, Oliver and Trueta (Fig. 3).

scholarly journals B cell Sirt1 deacetylates histone and non-histone proteins for epigenetic modulation of AID expression and the antibody response

2020 ◽  
Vol 6 (14) ◽  
pp. eaay2793 ◽  
Author(s):  
Huoqun Gan ◽  
Tian Shen ◽  
Daniel P. Chupp ◽  
Julia R. Taylor ◽  
Helia N. Sanchez ◽  
...  
Keyword(s):  
Antibody Response ◽  
B Cell ◽  
Histone Deacetylases ◽  
Somatic Hypermutation ◽  
Cytidine Deaminase ◽  
Dna Recombination ◽  
Sirtuin 1 ◽  
B Cell Differentiation ◽  
Class Iii ◽  
Nonhistone Proteins

Activation-induced cytidine deaminase (AID) mediates immunoglobulin class switch DNA recombination (CSR) and somatic hypermutation (SHM), critical processes for maturation of the antibody response. Epigenetic factors, such as histone deacetylases (HDACs), would underpin B cell differentiation stage–specific AID expression. Here, we showed that NAD+-dependent class III HDAC sirtuin 1 (Sirt1) is highly expressed in resting B cells and down-regulated by stimuli inducing AID. B cell Sirt1 down-regulation, deprivation of NAD+ cofactor, or genetic Sirt1 deletion reduced deacetylation of Aicda promoter histones, Dnmt1, and nuclear factor–κB (NF-κB) p65 and increased AID expression. This promoted class-switched and hypermutated T-dependent and T-independent antibody responses or led to generation of autoantibodies. Genetic Sirt1 overexpression, Sirt1 boost by NAD+, or allosteric Sirt1 enhancement by SRT1720 repressed AID expression and CSR/SHM. By deacetylating histone and nonhistone proteins (Dnmt1 and NF-κB p65), Sirt1 transduces metabolic cues into epigenetic changes to play an important B cell–intrinsic role in modulating antibody and autoantibody responses.

scholarly journals Sirtuins: Molecular Traffic Lights in the Crossroad of Oxidative Stress, Chromatin Remodeling, and Transcription

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Ramkumar Rajendran ◽  
Richa Garva ◽  
Marija Krstic-Demonacos ◽  
Constantinos Demonacos
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Transcriptional Regulation ◽  
Histone Deacetylases ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Class Iii ◽  
Nonhistone Proteins ◽  
Traffic Lights ◽  
Major Mechanism

Transcription is regulated by acetylation/deacetylation reactions of histone and nonhistone proteins mediated by enzymes called KATs and HDACs, respectively. As a major mechanism of transcriptional regulation, protein acetylation is a key controller of physiological processes such as cell cycle, DNA damage response, metabolism, apoptosis, and autophagy. The deacetylase activity of class III histone deacetylases or sirtuins depends on the presence of NAD+(nicotinamide adenine dinucleotide), and therefore, their function is closely linked to cellular energy consumption. This activity of sirtuins connects the modulation of chromatin dynamics and transcriptional regulation under oxidative stress to cellular lifespan, glucose homeostasis, inflammation, and multiple aging-related diseases including cancer. Here we provide an overview of the recent developments in relation to the diverse biological activities associated with sirtuin enzymes and stress responsive transcription factors, DNA damage, and oxidative stress and relate the involvement of sirtuins in the regulation of these processes to oncogenesis. Since the majority of the molecular mechanisms implicated in these pathways have been described for Sirt1, this sirtuin family member is more extensively presented in this paper.

scholarly journals Baseline HDAC6 and TFF3 proteins overexpression as prognostic markers of lupus nephritis relapse

2020 ◽  
Vol 9 (2) ◽  
pp. e14-e14
Author(s):  
Eman Hassan Abdelbary ◽  
Noha Farouk Ahmed ◽  
Adel Abdelmohsen Ghorab
Keyword(s):  
Lupus Nephritis ◽  
Serum Creatinine ◽  
Lupus Erythematosus ◽  
Kidney Diseases ◽  
Activity Index ◽  
Kidney Injury ◽  
Class Iii ◽  
Clinicopathologic Characteristics ◽  
Chronicity Index

Introduction: Lupus nephritis (LN) is a substantial manifestation of systemic lupus erythematosus (SLE). HDAC6 is overexpressed in various kidney diseases, and its inhibition slows kidney injury progression. Urinary TFF3 increases in chronic kidney diseases (CKDs) and may be associated with patient’s outcome. Objectives: This study aimed to examine the relationship between renal HDAC6 and TFF3 proteins expression and with clinicopathologic characteristics and outcome of LN. Patients and Methods: HDAC6 and TFF3 proteins’ expression was immunohistochemically detected in 56 cases of LN. They were correlated to patients’ age, gender, urinary 24 hours protein and serum creatinine levels at baseline and during follow up. Additionally, they were correlated to LN classes, activity index (AI) and chronicity index (CI) and relapse free survival (RFS). Results: HDAC6 overexpression was significantly associated with serum creatinine and 24 hours proteinuria levels at baseline (P = 0.041 and P =0.026 respectively) and during follow up (P < 0.001). It was associated with AI and CI of class III and IV LN (P = 0.047 and 0.003 respectively). TFF3 overexpression was associated with higher serum creatinine and more proteinuria at baseline (P = 0.015 and 0.001 respectively) and during follow up (P < 0.001). It was significantly associated with higher CI (P = 0.001). Both markers were associated with shorter RFS (P < 0.001). Conclusion: HDAC6 and TFF3 proteins are associated with clinicopathologic features of renal damage in LN. They are reliable predictors of patients’ RFS, which makes them good candidates for risk stratification of patients and targeted therapy.

Mammalian target of rapamycin and the kidney. II. Pathophysiology and therapeutic implications

2012 ◽  
Vol 303 (2) ◽  
pp. F180-F191 ◽  
Author(s):  
Wilfred Lieberthal ◽  
Jerrold S. Levine
Keyword(s):  
Animal Studies ◽  
Kidney Diseases ◽  
Mammalian Target Of Rapamycin ◽  
Graft Function ◽  
Kidney Injury ◽  
Cyst Formation ◽  
Renal Diseases ◽  
Therapeutic Implications ◽  
The Metabolic Syndrome ◽  
Renal Regeneration

The mTOR pathway plays an important role in a number of common renal diseases, including acute kidney injury (AKI), diabetic nephropathy (DN), and polycystic kidney diseases (PKD). The activity of mTOR complex 1 (mTORC1) is necessary for renal regeneration and repair after AKI, and inhibition of mTORC1 by rapamycin has been shown to delay recovery from ischemic AKI in animal studies, and to prolong delayed graft function in humans who have received a kidney transplant. For this reason, administration of rapamycin should be delayed or discontinued in patients with AKI until full recovery of renal function has occurred. On the other hand, inappropriately high mTORC1 activity contributes to the progression of the metabolic syndrome, the development of type 2 diabetes, and the pathogenesis of DN. In addition, chronic hyperactivity of mTORC1, and possibly also mTORC2, contributes to cyst formation and enlargement in a number of forms of PKD. Inhibition of mTOR, using either rapamycin (which inhibits predominantly mTORC1) or “catalytic” inhibitors (which effectively inhibit both mTORC1 and mTORC2), provide exciting possibilities for novel forms of treatment of DN and PKD. In this second part of the review, we will examine the role of mTOR in the pathophysiology of DN and PKD, as well as the potential utility of currently available and newly developed inhibitors of mTOR to slow the progression of DN and/or PKD.

scholarly journals Nephrotoxicity of Herbal Products in Europe—A Review of an Underestimated Problem of Nephrotoxicity of Herbal Products

2021 ◽  
Vol 22 (8) ◽  
pp. 4132
Author(s):  
Katarzyna Kiliś-Pstrusińska ◽  
Anna Wiela-Hojeńska
Keyword(s):  
Kidney Diseases ◽  
Herbal Medicines ◽  
Kidney Injury ◽  
Herbal Products ◽  
Chronic Kidney Diseases ◽  
European Origin ◽  
Synthetic Drugs ◽  
The Many ◽  
Pharmacologically Active ◽  
Traditional Chinese Herbal Medicines

Currently in Europe, despite the many advances in production technology of synthetic drugs, the interest in natural herbal medicines continues to increase. One of the reasons for their popular use is the assumption that natural equals safe. However, herbal medicines contain pharmacologically active ingredients, some of which have been associated with adverse effects. Kidneys are particularly susceptible to injury induced by toxins, including poisonous constituents from medicinal plants. The most recognized herb-induced kidney injury is aristolochic acid nephropathy connected with misuse of certain Traditional Chinese herbal medicines. Data concerning nephrotoxicity of plant species of European origin are scarce. Here, we critically review significant data of the nephrotoxicity of several plants used in European phytotherapy, including Artemisia herba-alba, Glycyrrhiza glabra, Euphorbia paralias, and Aloe). Causative mechanisms and factors predisposing to intoxications from the use of herbs are discussed. The basic intention of this review is to improve pharmacovigilance of herbal medicine, especially in patients with chronic kidney diseases.

scholarly journals Renal Manifestations of Covid-19: Physiology and Pathophysiology

2021 ◽  
Vol 10 (6) ◽  
pp. 1216
Author(s):  
Zaher Armaly ◽  
Safa Kinaneh ◽  
Karl Skorecki
Keyword(s):  
Viral Replication ◽  
Virus Disease ◽  
Multiorgan Failure ◽  
Critical Role ◽  
Kidney Injury ◽  
Small Sample ◽  
Renal Physiology ◽  
High Morbidity ◽  
Enzymatic Production ◽  
High Incidence

Corona virus disease 2019 (COVID-19) imposes a serious public health pandemic affecting the whole world, as it is spreading exponentially. Besides its high infectivity, SARS-CoV-2 causes multiple serious derangements, where the most prominent is severe acute respiratory syndrome as well as multiple organ dysfunction including heart and kidney injury. While the deleterious impact of SARS-CoV-2 on pulmonary and cardiac systems have attracted remarkable attention, the adverse effects of this virus on the renal system is still underestimated. Kidney susceptibility to SARS-CoV-2 infection is determined by the presence of angiotensin-converting enzyme 2 (ACE2) receptor which is used as port of the viral entry into targeted cells, tissue tropism, pathogenicity and subsequent viral replication. The SARS-CoV-2 cellular entry receptor, ACE2, is widely expressed in proximal epithelial cells, vascular endothelial and smooth muscle cells and podocytes, where it supports kidney integrity and function via the enzymatic production of Angiotensin 1-7 (Ang 1-7), which exerts vasodilatory, anti-inflammatory, antifibrotic and diuretic/natriuretic actions via activation of the Mas receptor axis. Loss of this activity constitutes the potential basis for the renal damage that occurs in COVID-19 patients. Indeed, several studies in a small sample of COVID-19 patients revealed relatively high incidence of acute kidney injury (AKI) among them. Although SARS-CoV-1 -induced AKI was attributed to multiorgan failure and cytokine release syndrome, as the virus was not detectable in the renal tissue of infected patients, SARS-CoV-2 antigens were detected in kidney tubules, suggesting that SARS-CoV-2 infects the human kidney directly, and eventually induces AKI characterized with high morbidity and mortality. The mechanisms underlying this phenomenon are largely unknown. However, the fact that ACE2 plays a crucial role against renal injury, the deprivation of the kidney of this advantageous enzyme, along with local viral replication, probably plays a central role. The current review focuses on the critical role of ACE2 in renal physiology, its involvement in the development of kidney injury during SARS-CoV-2 infection, renal manifestations and therapeutic options. The latter includes exogenous administration of Ang (1-7) as an appealing option, given the high incidence of AKI in this ACE2-depleted disorder, and the benefits of ACE2/Ang1-7 including vasodilation, diuresis, natriuresis, attenuation of inflammation, oxidative stress, cell proliferation, apoptosis and coagulation.

scholarly journals CD73 Overexpression in Podocytes: A Novel Marker of Podocyte Injury in Human Kidney Disease

2021 ◽  
Vol 22 (14) ◽  
pp. 7642
Author(s):  
Zoran V. Popovic ◽  
Felix Bestvater ◽  
Damir Krunic ◽  
Bernhard K. Krämer ◽  
Raoul Bergner ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Membranous Glomerulonephritis ◽  
Human Kidney ◽  
Protective Role ◽  
Control Group ◽  
Podocyte Injury ◽  
Ccr2 Expression ◽  
Cd73 Expression

The CD73 pathway is an important anti-inflammatory mechanism in various disease settings. Observations in mouse models suggested that CD73 might have a protective role in kidney damage; however, no direct evidence of its role in human kidney disease has been described to date. Here, we hypothesized that podocyte injury in human kidney diseases alters CD73 expression that may facilitate the diagnosis of podocytopathies. We assessed the expression of CD73 and one of its functionally important targets, the C-C chemokine receptor type 2 (CCR2), in podocytes from kidney biopsies of 39 patients with podocytopathy (including focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous glomerulonephritis (MGN) and amyloidosis) and a control group. Podocyte CD73 expression in each of the disease groups was significantly increased in comparison to controls (p < 0.001–p < 0.0001). Moreover, there was a marked negative correlation between CD73 and CCR2 expression, as confirmed by immunohistochemistry and immunofluorescence (Pearson r = −0.5068, p = 0.0031; Pearson r = −0.4705, p = 0.0313, respectively), thus suggesting a protective role of CD73 in kidney injury. Finally, we identify CD73 as a novel potential diagnostic marker of human podocytopathies, particularly of MCD that has been notorious for the lack of pathological features recognizable by light microscopy and immunohistochemistry.

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

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