4.7 Article

2,8-Dihydroxyadenine-induced nephropathy causes hexosylceramide accumulation with increased mTOR signaling, reduced levels of protective SirT3 expression and impaired renal mitochondrial function

Related references

Note: Only part of the references are listed.
Article Cardiac & Cardiovascular Systems

Long- and very long-chain ceramides are predictors of acute kidney injury in patients with acute coronary syndrome: the PEACP study

Lianjing Liang et al.

Summary: This study evaluated the relationship between plasma ceramide levels and acute kidney injury (AKI) in patients with acute coronary syndrome (ACS). The study found that levels of certain ceramides were independently associated with AKI risk. These results suggest that long-chain and very-long-chain ceramide levels may help determine high AKI risk beyond traditional assessments.

CARDIOVASCULAR DIABETOLOGY (2023)

Article Cardiac & Cardiovascular Systems

Accelerated Vascular Aging in Chronic Kidney Disease: The Potential for Novel Therapies

S. Hobson et al.

Summary: The pathophysiology of vascular disease is associated with accelerated biological aging and a combination of various risk factors. Chronic kidney disease (CKD) serves as a valuable model to study the structural, functional, and molecular aspects of arterial aging. The cardiorenal syndrome results from the detrimental interaction between the kidney and the cardiovascular system. Understanding the molecular mechanisms of uremic early vascular aging provides insights into inflammatory pathways and emerging risk factors, offering new prospects for pharmacological and nutritional interventions.

CIRCULATION RESEARCH (2023)

Article Cardiac & Cardiovascular Systems

The Cardio-Kidney Patient: Epidemiology, Clinical Characteristics and Therapy

Katharina Schuett et al.

Summary: Patients with CKD are at high risk for cardiovascular diseases like coronary artery disease, heart failure, arrhythmias, and sudden cardiac death. The presence of CKD also affects the prognosis of patients with cardiovascular disease, leading to increased morbidity and mortality. Treatment options for cardiovascular disease in advanced CKD patients are limited, and trials often exclude these patients. Therefore, strategies for treating cardiovascular disease in CKD patients are extrapolated from trials conducted in patients without CKD. This article summarizes the epidemiology, clinical presentation, and treatment options for cardiovascular disease in CKD, and discusses available treatment options to reduce morbidity and mortality in this high-risk population.

CIRCULATION RESEARCH (2023)

Article Medical Laboratory Technology

High-Density Lipoprotein Lipidomics in Chronic Kidney Disease

Benjamin Lidgard et al.

Summary: Patients with chronic kidney disease (CKD) have dysfunctional high-density lipoprotein (HDL) particles. This study investigated the association of estimated glomerular filtration rate (eGFR) and albuminuria with the lipid composition of HDL in CKD patients. The results showed that albuminuria was significantly associated with specific alterations in the lipid composition of HDL.

CLINICAL CHEMISTRY (2023)

Review Physiology

How Many Cell Types Are in the Kidney and What Do They Do?

Michael S. Balzer et al.

Summary: The kidney plays a crucial role in maintaining electrolyte, water, and acid-base balance, regulating blood pressure, and eliminating waste compounds. Different specialized cell types in the kidney work together to ensure its proper function. With the advancement of single-cell technologies, we now have new opportunities to classify kidney cells and understand their functions.

ANNUAL REVIEW OF PHYSIOLOGY (2022)

Article Urology & Nephrology

A systematic review and meta-analysis of murine models of uremic cardiomyopathy

Josefin Soppert et al.

Summary: Chronic kidney disease (CKD) increases the risk of developing uremic cardiomyopathy, and animal studies are used to investigate the underlying mechanisms. This review systematically analyzed 88 studies and performed meta-analyses of 52 to identify suitable animal models for future experimental studies. The results showed variations in different mouse strains and the effects of CKD on cardiac hypertrophy, fibrosis, and function. Multifactorial hit models consistently induced cardiac hypertrophy and fibrosis compared to single hit kidney injury models.

KIDNEY INTERNATIONAL (2022)

Review Biochemistry & Molecular Biology

Crosstalk between Mitochondrial Protein Import and Lipids

Juliane J. Hoffmann et al.

Summary: Mitochondria import precursor proteins from cytosol through translocase complexes. The phospholipid composition of mitochondrial membranes affects the stability and activity of protein translocases, as well as the rearrangement and distortion of lipid bilayer during protein integration. Phospholipids also play a critical role in respiratory chain activity and membrane potential generation for protein import. The close link between outer membrane protein translocases and lipid trafficking at contact sites further controls mitochondrial biogenesis.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

Article Biochemistry & Molecular Biology

Uremic Myopathy and Mitochondrial Dysfunction in Kidney Disease

Eurico Serrano et al.

Summary: Alterations in muscle structure and function in chronic kidney disease (CKD) are associated with poor outcomes. This study found that changes in mitochondrial metabolism, specifically decreased oxidative metabolism and increased glycolysis and fatty acid oxidation, contribute to muscle dysfunction in CKD.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

Article Endocrinology & Metabolism

The sodium-glucose co-transporter-2 inhibitor ertugliflozin modifies the signature of cardiac substrate metabolism and reduces cardiac mTOR signalling, endoplasmic reticulum stress and apoptosis

Julia Moellmann et al.

Summary: This study aimed to investigate the cardiac signalling pathways connecting substrate utilization with left ventricular remodelling in a murine pressure overload model. The results showed that SGLT2 inhibition with ertugliflozin improved left ventricular function and reduced myocardial fibrosis, potentially through reduced cardiac insulin and increased AMPK signalling. This reduction in fibrosis was associated with less cardiac mTOR activation, alleviation of ER stress and apoptosis.

DIABETES OBESITY & METABOLISM (2022)

Article Biochemistry & Molecular Biology

Pro-oxidative priming but maintained cardiac function in a broad spectrum of murine models of chronic kidney disease

Julia Wollenhaupt et al.

Summary: CKD increases cardiac oxidative stress responses in the heart, but additional hits are required to induce uremic cardiomyopathy.

REDOX BIOLOGY (2022)

Article Biochemistry & Molecular Biology

Expression Profiles of Kidney Mitochondrial Proteome during the Progression of the Unilateral Ureteral Obstruction: Focus on Energy Metabolism Adaptions

Ariadna Jazmin Ortega-Lozano et al.

Summary: The study examined the impact of UUO at different time points on the mitochondrial proteome of rat kidneys, revealing changes in proteins related to oxidative phosphorylation, the tricarboxylic acid cycle, and fatty acid metabolism, all of which are associated with bioenergetics during ON.

METABOLITES (2022)

Article Medicine, Research & Experimental

Empagliflozin reduces kidney fibrosis and improves kidney function by alternative macrophage activation in rats with 5/6-nephrectomy

Yong-Ping Lu et al.

Summary: Empagliflozin treatment significantly reduced BUN, creatinine, urinary albumin excretion, renal interstitial fibrosis, and glomerulosclerosis. Single-cell RNA sequencing revealed CD206+CD68+ M2 macrophages highly expressed fibrosis-promoting genes, and Empagliflozin inhibited their polarization by affecting mitophagy and mTOR pathways.

BIOMEDICINE & PHARMACOTHERAPY (2022)

Article Biochemistry & Molecular Biology

Upregulation of the serine palmitoyltransferase subunit SPTLC2 by endoplasmic reticulum stress inhibits the hepatic insulin response

Goon-Tae Kim et al.

Summary: The study found that ER stress can regulate the de novo biosynthesis of sphingolipids through the activation of serine palmitoyltransferase, leading to negative effects on hepatic insulin response. Understanding the mechanisms underlying insulin resistance is crucial for new treatments for metabolic diseases such as diabetes.

EXPERIMENTAL AND MOLECULAR MEDICINE (2022)

Review Biochemistry & Molecular Biology

A Rheostat of Ceramide and Sphingosine-1-Phosphate as a Determinant of Oxidative Stress-Mediated Kidney Injury

Norishi Ueda

Summary: Reactive oxygen species (ROS) play a role in regulating sphingolipid metabolism, affecting apoptosis, survival, cell proliferation, inflammation, and fibrosis in the kidney. The balance of ceramide and sphingosine-1-phosphate (S1P) is regulated by ROS-antioxidant interactions, which impact mitochondrial function, Bcl-2 family proteins, calcium homeostasis, and signaling pathways.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

Article Medicine, Research & Experimental

Impaired muscle mitochondrial energetics is associated with uremic metabolite accumulation in chronic kidney disease

Trace Thome et al.

Summary: This study investigated the mechanisms of skeletal muscle mitochondrial impairment in mice with adenine-induced CKD. It found reductions in mitochondrial oxidative phosphorylation and identified unknown uremic metabolites associated with the degree of mitochondrial impairment. Additionally, CKD mice showed muscle atrophy, protein degradation, and morphological changes in the neuromuscular junction.

JCI INSIGHT (2021)

Article Biochemistry & Molecular Biology

Oxidative stress increases 1-deoxysphingolipid levels in chronic kidney disease

Ting Gui et al.

Summary: Chronic kidney disease leads to dyslipidemia through changes in lipid metabolism, ultimately contributing to disease progression and cardiovascular complications. Analysis of lipid metabolites in CKD models and patients revealed an increase in 1-deoxysphingolipids, which was directly correlated with oxidative stress levels in the kidneys.

FREE RADICAL BIOLOGY AND MEDICINE (2021)

Article Biochemistry & Molecular Biology

The Dysregulation of Eicosanoids and Bile Acids Correlates with Impaired Kidney Function and Renal Fibrosis in Chronic Renal Failure

Yan-Ni Wang et al.

Summary: Chronic renal failure is characterized by metabolic disturbances, particularly dyslipidemia, and profound changes in lipid and lipoprotein metabolism. Studies have shown that leukotrienes and bile acids are strongly correlated with serum creatinine levels in CRF. Treatment with Polyporus umbellatus and ergone can significantly improve lipid abnormalities associated with CRF.

METABOLITES (2021)

Article Cardiac & Cardiovascular Systems

Cardiovascular Disease in Chronic Kidney Disease Pathophysiological Insights and Therapeutic Options

Joachim Jankowski et al.

Summary: Patients with chronic kidney disease face an increased risk of cardiovascular events, with advanced CKD stages significantly elevating the risk. Cardiovascular events, rather than end-stage kidney disease, are the leading cause of death in this high-risk population, and CKD causes a proinflammatory state that affects the cardiovascular system.

CIRCULATION (2021)

Review Physiology

The Crucial Roles of Phospholipids in Aging and Lifespan Regulation

Yucan Dai et al.

Summary: Phospholipids, as major membrane lipids, play important roles in protecting cells, promoting cellular processes, and are linked to signal transductions, organelle functions, physiological processes, and human diseases. Recent studies have shown crucial roles of membrane lipids in the aging process, with investigations on changing patterns of phospholipid species with age and their functions in regulating healthspan and lifespan. This advances our understanding of the relationship between membrane lipids and aging.

FRONTIERS IN PHYSIOLOGY (2021)

Article Physiology

Skeletal myopathy in CKD: a comparison of adenine-induced nephropathy and 5/6 nephrectomy models in mice

Kyoungrae Kim et al.

Summary: In this study, adenine-induced nephropathy and 5/6 nephrectomy models of chronic kidney disease were compared, showing equivalent levels of muscle atrophy and mitochondrial impairment. The adenine model exhibited lower mortality rates, higher consistency in uremic toxin levels, and dysregulated phosphate homeostasis compared with the 5/6 nephrectomy model.

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY (2021)

Review Urology & Nephrology

Lipoproteins and fatty acids in chronic kidney disease: molecular and metabolic alterations

Heidi Noels et al.

Summary: Chronic kidney disease (CKD) leads to alterations in lipid and lipoprotein metabolism, affecting cardiovascular health. These changes can trigger inflammatory and atherogenic processes, potentially impacting both heart and kidney health.

NATURE REVIEWS NEPHROLOGY (2021)

Review Cardiac & Cardiovascular Systems

Uraemic Cardiomyopathy: A Review of Current Literature

Kartheek Garikapati et al.

Summary: Uraemic Cardiomyopathy (UC) is a complex disease associated with End-Stage Renal Disease (ESRD) that poses significant cardiovascular risks. Diagnosis requires multi-modality imaging techniques, and treatment options are limited, emphasizing the need for ongoing research for further therapies.

CLINICAL MEDICINE INSIGHTS-CARDIOLOGY (2021)

Article Urology & Nephrology

Cellular and Molecular Mechanisms of Kidney Injury in 2,8-Dihydroxyadenine Nephropathy

Barbara Mara Klinkhammer et al.

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY (2020)

Article Cell Biology

Glycosphingolipid metabolism and polycystic kidney disease

Thomas A. Natoli et al.

CELLULAR SIGNALLING (2020)

Article Biochemistry & Molecular Biology

Empagliflozin improves left ventricular diastolic function of db/db mice

Julia Moellmann et al.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE (2020)

Review Urology & Nephrology

Mitochondrial dysfunction in kidney injury, inflammation, and disease: potential therapeutic approaches

Divya Bhatia et al.

KIDNEY RESEARCH AND CLINICAL PRACTICE (2020)

Review Urology & Nephrology

mTOR Signaling in Kidney Diseases

Yuan Gui et al.

KIDNEY360 (2020)

Review Pharmacology & Pharmacy

Inflammation and renal fibrosis: Recent developments on key signaling molecules as potential therapeutic targets

Wenshan Lv et al.

EUROPEAN JOURNAL OF PHARMACOLOGY (2018)

Review Medicine, Research & Experimental

Endoplasmic reticulum stress in the pathogenesis of fibrotic disease

Jonathan A. Kropski et al.

JOURNAL OF CLINICAL INVESTIGATION (2018)

Article Urology & Nephrology

A novel model of reno-cardiac syndrome in the C57BL/ 6 mouse strain

Julius E. Kieswich et al.

BMC NEPHROLOGY (2018)

Review Urology & Nephrology

Pharmacologic Approaches to Improve Mitochondrial Function in AKI and CKD

Hazel H. Szeto

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY (2017)

Review Urology & Nephrology

The hallmarks of mitochondrial dysfunction in chronic kidney disease

Daniel L. Galvan et al.

KIDNEY INTERNATIONAL (2017)

Review Urology & Nephrology

Mitochondrial energetics in the kidney

Pallavi Bhargava et al.

NATURE REVIEWS NEPHROLOGY (2017)

Article Oncology

mTORC2 Promotes Tumorigenesis via Lipid Synthesis

Yakir Guri et al.

CANCER CELL (2017)

Article Biochemistry & Molecular Biology

Acid Sphingomyelinase Promotes Endothelial Stress Response in Systemic Inflammation and Sepsis

Ha-Yeun Chung et al.

MOLECULAR MEDICINE (2016)

Review Urology & Nephrology

Roles of mTOR complexes in the kidney: implications for renal disease and transplantation

Daniel Fantus et al.

NATURE REVIEWS NEPHROLOGY (2016)

Article Biochemistry & Molecular Biology

Glycosphingolipids and cell death: one aim, many ways

Carmen Garcia-Ruiz et al.

APOPTOSIS (2015)

Article Cell Biology

Reversal of Mitochondrial Transhydrogenase Causes Oxidative Stress in Heart Failure

Alexander G. Nickel et al.

CELL METABOLISM (2015)

Review Transplantation

Potential role of Akt signaling in chronic kidney disease

Aiping Lan et al.

NEPHROLOGY DIALYSIS TRANSPLANTATION (2015)

Article Multidisciplinary Sciences

mTORC1 maintains renal tubular homeostasis and is essential in response to ischemic stress

Florian Grahammer et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2014)

Review Endocrinology & Metabolism

Podocyte pathology and nephropathy - sphingolipids in glomerular diseases

Sandra Merscher et al.

FRONTIERS IN ENDOCRINOLOGY (2014)

Review Cell Biology

Where is mTOR and what is it doing there?

Charles Betz et al.

JOURNAL OF CELL BIOLOGY (2013)

Article Geriatrics & Gerontology

Instability of the cellular lipidome with age

Jessica R. Hughes et al.

Article Urology & Nephrology

Secular Trends in Cardiovascular Mortality Rates of Patients Receiving Dialysis Compared With the General Population

Matthew A. Roberts et al.

AMERICAN JOURNAL OF KIDNEY DISEASES (2011)

Review Cell Biology

Principles of bioactive lipid signalling: lessons from sphingolipids

Yusuf A. Hannun et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2008)