Aryl Hydrocarbon Receptor Mediates Indoxyl Sulfate-Induced Cellular Senescence in Human Umbilical Vein Endothelial Cells
スポンサーリンク
概要
- 論文の詳細を見る
Aim: Vascular senescence, which is accelerated in individuals with chronic kidney disease (CKD), contributes to the development of cardio-renal syndrome, and various uremic toxins may play important roles in the mechanisms underlying this phenomenon. We recently reported that indoxyl sulfate (IS), a uremic toxin, directly activates aryl hydrocarbon receptor (AhR) and generates oxidative stress through NADPH oxidase-4 in human umbilical vein endothelial cells (HUVECs). In the current study, we sought to examine whether IS regulates sirtuin 1 (Sirt1) and affects endothelial senescence via AhR activation.Methods: HUVECs were incubated with 500 μmol/L of IS for the indicated time periods. In order to evaluate changes in the senescence of the HUVECs, the number of senescence-associated β-galactosidase (SA β-gal)-positive cells was determined using an image analysis software program. The intracellular nicotinamide phosphoribosyltransferase (iNampt) activity, cellular NAD＋/NADPH ratio and Sirt1 activity were analyzed according to a colorimetric assay to determine the mechanism of cellular senescence. Furthermore, we evaluated the involvement of AhR in the senescence-related changes induced by IS using AhR antagonists.Results: IS decreased the iNampt activity, NAD＋/NADPH ratio and Sirt1 activity, resulting in an increase in the percentage of SA β-gal-positive cells. On the other hand, the AhR antagonists restored the IS-induced decrease in the NAD＋ content in association with an improvement in the iNampt activity and ameliorated the senescence-related changes. Taken together, these results indicate that IS impairs the iNampt-NAD＋-Sirt1 system via AhR activation, which in turn promotes endothelial senescence.Conclusions: The IS-AhR pathway induces endothelial senescence. Therefore, blocking the effects of AhR in the endothelium may provide a new therapeutic tool for treating cardio-renal syndrome.
- 一般社団法人 日本動脈硬化学会の論文
著者
-
Ikeda Takanori
Department Of Cardiovascular Medicine Graduate School Of Medicine Kyoto University
-
Tatebe Junko
Department Of Laboratory Medicine Toho University
-
Watanabe Ippei
Department Of Applied Environmental Biology Graduate School Of Pharmaceutical Sciences Osaka Univers
-
Morita Toshisuke
Department Of Laboratory Medicine Toho University
-
Yamazaki Junichi
Department Of Biofunctional Science Faculty Of Agriculture And Life Science Hirosaki University
-
Morita Toshisuke
Department of Laboratory Medicine, Toho University Faculty of Medicine
-
Koizumi Masayuki
Department of Cardiovascular Medicine, Toho University Faculty of Medicine
関連論文
- Effects of Intravenous Nifekalant as a Lifesaving Drug for Severe Ventricular Tachyarrhythmias Complicating Acute Coronary Syndrome
- PJ-577 The Antiplatelet Effect of Aspirin does not Change after 2-year Interval(PJ097,Cardiovascular Pharmacology (Clinical) (H),Poster Session (Japanese),The 73rd Annual Scientific Meeting of The Japanese Circulation Society)
- 1 Three-Year Outcome of the PRospective Evaluation of VENtricular Tachyarrhythmic Events and Sudden Cardiac Death in Patients with Left Ventricular Dysfunction (PREVENT-SCD) Study(Late Breaking Clinical Trials I,The 73rd Annual Scientific Meeting of The J
- Clopidogrel Resistance in Japanese Patients Scheduled for Percutaneous Coronary Intervention(Ischemic Heart Disease)
- Evaluation of the Antiplatelet Effects of Cilostazol, a Phosphodiesterase 3 Inhibitor, by VASP Phosphorylation and Platelet Aggregation
- PJ-422 Platelet Aggregability under Aspirin Therapy in Smoker is Higher than That in Non-smoker(Cardiovascular pharmacology, basic/clinical(05)(H),Poster Session(Japanese),The 72nd Annual Scientific Meeting of the Japanese Circulation Society)
- PJ-421 Anti-platelet Effects of Statins in Patients under Aspirin Therapies(Cardiovascular pharmacology, basic/clinical(05)(H),Poster Session(Japanese),The 72nd Annual Scientific Meeting of the Japanese Circulation Society)
- 5 Interim analyses of PRospective Evaluation of VENtricular Tachyarrhythmic events and Sudden Cardiac Death in patients with left ventricular dysfunction (PREVENT-SCD) study(Late Breaking Clinical Trials II,Special Program,The 72nd Annual Scientific Meeti
- Differences in Vagal and Sympathetic Effects on Excitation Wave Dynamics of Paroxysmal Atrial Fibrillation : A Simulation Study
- Importance of Wavefront Organization and Widened Excitable Gap in Terminating Atrial Fibrillation by Pilsicainide
- Assessment of Atrioventricular Nodal Electrophysiological Characteristics After Radiofrequency Catherter Ablation of the Slow Pathway in Atrioventricular Nodal Reentrant Tachycardia : 3-Month Follow up
- -P239- THREE MONTHS FOLLOW-UP ASSESSMENT OF AV NODAL PHYSIOLOGY AFTER RADIOFREQUENCY CATHETER ABLATION OF SLOW PATHWAY IN AV NODAL REENTRANT TACHYCARDIA COMPARISON WITH WPW SYNDROME(PROCEEDINGS OF THE 59th ANNUAL SCIENTIFIC MEETING OF THE JAPANESE CIRCULA
- Dielectric effect during catheter ablation with microwave energy application in a myocardial phantom model
- RELATION BETWEEN THE SIZE OF LESIONS AND ARRHYTHMIAS PRODUCED BY MICROWAVE CATHETER ABLATION WITH A SPECIAL ELECTRODE DEVICE
- OPTIMAL FREQUENCY OF RADIOFREQUENCY CATHETER ABLATION IN VITRO AND IN VIVO FOR TREATING VENTRICULAR TACHYCARDIAS : A study using various frequencies
- WITHDRAWAL OF LONG-TERM ANTIARRHYTHMIC TREATMENT IN PATIENTS WITH FREQUENT VENTRICULAR ARRHYTHMIAS
- CLINICAL STUDY OF FREQUENCY DOMAIN ANALYSIS WITH USE OF THE P WAVE TRIGGERED SIGNAL-AVERAGED ELECTROCARDIOGRAMS FOR PREDICTING IN PATIENTS WITH PAROXYSMAL ATRIRIAL FIBRILLATION
- EVALIATION OF ARRHYTHMOGENICITY AND ABLATED LESION OF CATHETER ABLATION USING MICROWAVE ENERGY
- -0274-AN EXPERIMENTAL STUDY OF THE INFLUENCE ON THE MYOCARDIAL TISSUE AND ON THE TRICUSPID VENTRICULAR BLOCK BY RADIOFREQUENCY CATHETER ABLATION
- PJ-500 Coronary Artery Affects the Wave Propagation in a Thin Ventricular Myocardium : Study by the Optical Mapping and Computer Graphics Techniques(Arrhythmia, Basic 6 (A) : PJ84)(Poster Session (Japanese))
- Characterization of the Antiplatelet Effect of Aspirin at Enrollment and After 2-Year Follow-up in a Real Clinical Setting in Japan
- The Time Course of Recovery of Left Atrial Appendage Function Following Reversion of Chronic Atrial Flutter to Sinus Rhythm
- PE-491 Assessment of Circadian Variation in the Occurrence of Out-of-Hospital Cardiopulmonary Arrest with a Large Number of Japanese Patients(PE082,Ventricular Arrhythmia (Clinical/Diagnosis/Treatment) (A),Poster Session (English),The 73rd Annual Scientif
- DPJ-038 Physiological Pacing Site in the Right Ventricle : Alternative Mid-Septal Pacing is Superior Compered to Conventional Apical Pacing(DPJ07,Arrhythmia, Others (Clinical/Diagnosis/Treatment) 2 (A),Digital Poster Session (Japanese),The 73rd Annual Sci
- OE-372 Heart Rate Turbulence as a Predictor of Cardiac Mortality and Arrhythmic Events in Patients with Ischemic or Nonischemic Dilated Cardiomyopathy(OE63,ECG/Body Surface Potential Mapping/Holter 1 (A),Oral Presentation (English),The 73rd Annual Scienti
- OE-243 Pathophysiology of the J Wave in Patients with Idiopathic Ventricular Fibrillation : Repolarization Abnormalities versus Conduction Disturbances(OE41,Ventricular Arrhythmia, Treatment (A),Oral Presentation (English),The 73rd Annual Scientific Meeti
- OE-120 Time-Domain T -Wave Alternans Measured from Holter Electrocardiograms Predicts Cardiac Mortality in Patients with Left Ventricular Dysfunction : A Prospective Study(OE21,ECG/Body Surface Potential Mapping/Holter 2 (A),Oral Presentation (English),Th
- PJ-771 J Waves on 12-Lead Electrocardiogram : Comparison between Patients with Syncope and Healthy Subjects(Arrhythmia, diagnosis / Pathophysiology / EPS(11)(A),Poster Session(Japanese),The 72nd Annual Scientific Meeting of the Japanese Circulation Societ
- PJ-300 Visible T-Waves Variation after Treadmill Exercise Testing Predicts Cardiac Mortality in Post-Myocardial Infarction Patients with Preserved Cardiac Function(Exercise test/Cardiac rehabilitation(06)(H),Poster Session(Japanese),The 72nd Annual Scient
- PE-320 Assessment of Heart Rate Turbulence Determined on Holter Electrocardiogram in Predicting Future Cardiac Events : A Single Center Follow-up Study(ECG/Body surface potential mapping/Holter(04)(A),Poster Session(English),The 72nd Annual Scientific Mee
- OJ-026 Selective Site Pacing in the Right Ventricle : First Report of Pacing from Mid-Septum in Japan(Arrhythmia, therapy(05)(A),Oral Presentation(Japanese),The 72nd Annual Scientific Meeting of the Japanese Circulation Society)
- OE-376 Evaluation of Right Ventricular Scar and Function Using Contrast-Enhanced Magnetic Resonance Imaging in Idiopathic Dilated Cardiomyopathy : Insight into Device Therapy(MRI/MRA(01)(I),Oral Presentation(English),The 72nd Annual Scientific Meeting of
- OE-279 Time-Domain T-Wave Alternans Predicts Cardiac Mortality in a Population Undergoing 24-Hour Holter Electrocardiogram : A Prospective Study(ECG/Body surface potential mapping/Holter(01)(A),Oral Presentation(English),The 72nd Annual Scientific Meeting
- 2 Risk Stratification Techniques for Sudden Cardiac Death in Patients with a Brugada-Type Electrocardiogram(Symposium 5 (SY-05) (A) New Findings of Mechanism and Therapeutic Strategies of Idiopathic Ventricular Fibrillation,Special Program,The 72nd Annual
- Risk Stratification for Sudden Cardiac Death(Ventricular Tachycardia/Fibrillation)
- PJ-289 Nifekalant Decreases Defibrillation Threshold of Electrical Cardioversion in Patients with Persistent Atrial Fibrillation(Arrhythmia, therapy-19, The 71st Annual Scientific Meeting of the Japanese Circulation Society)
- PJ-280 Myocardial Scar Detected by Contrast-Enhanced Magnetic Resonance Imaging and Arrhythmic Risk Stratification Markers in Patients with Nonischemic Cardiomyopathy(Arrhythmia, diagnosis/pathophysiology/EPS-13, The 71st Annual Scientific Meeting of the
- PE-048 Absence of Correlation between Spectral Method and Newly Developed Ambulatory Electrocardiogram-Based Time-Domain Method of T-Wave Alternans(ECG/Body surface potential mapping/Holter-3, The 71st Annual Scientific Meeting of the Japanese Circulation
- PE-028 Circadian Variation in the Occurrence of Out-of-Hospital Cardiopulmonary Arrest in a Japanese Population(Arrhythmia, diagnosis/pathophysiology/EPS-06, The 71st Annual Scientific Meeting of the Japanese Circulation Society)
- FRS-108 Identifying the Origin of Ventricular Arrhythmias Using 3D-Echocardiographic Tissue Tracking Imaging(Recent Advance in Cardiac Ultrasound, The 71st Annual Scientific Meeting of the Japanese Circulation Society)
- Importance of V5R ST-elevation to Detect Right Ventricular Myocardial Infarction : Evaluation by Using Cardiac Magnetic Resonance Imaging(X-ray/CT/MRI/DSA 7 (I), The 69th Annual Scientific Meeting of the Japanese Circulation Society)
- PJ-274 Discrepancy of Necrosis Size and Transmural Extent in Small-Sized Myocardial Infarction Evaluated by Contrast-Enhanced Magnetic Resonance Imaging(X-ray/CT/MRI/DSA5 (I) : PJ46)(Poster Session (Japanese))
- PJ-273 Visualization of Ventricular Thrombi With Contrast-Enhanced Magnetic Resonance Imaging in Patients With an Anterior-Apical Myocardial Infarction(X-ray/CT/MRI/DSA5 (I) : PJ46)(Poster Session (Japanese))
- Effects of Landiolol, an Ultra-Short-Acting β_1-Selective Blocker, on Electrical Storm Refractory to Class III Antiarrhythmic Drugs
- Quantitative assessment of cibenzoline administration for vagally mediated paroxysmal atrial fibrillation using frequency-domain heart rate variability analysis
- PE-024 Prevalence of Brugada-Type Electrocardiograms with Class IC Antiarrhythmic Drugs in Patients with Paroxysmal Atrial Tachyarrhythmias : Pilsicainide versus Propafenone(Arrhythmia, diagnosis/pathophysiology/EPS-05, The 71st Annual Scientific Meeting
- PE-020 Noninvasive Strategies in Unmasking Brugada Syndrome : Full Stomach Test versus Pharmacological Test(Arrhythmia, diagnosis/pathophysiology/EPS-05, The 71st Annual Scientific Meeting of the Japanese Circulation Society)
- PJ-276 Lower Efficacy of Aspirin in Diabetic Patients(Thromboembolism/Antithrombotic therapy/Thrombolysis-5, The 71st Annual Scientific Meeting of the Japanese Circulation Society)
- PE-178 GDP/GTP Cycle of Rab27 is Regulated by Constitutive GDP/GTP Exchange Activity and Secretion-dependent GTP Hydrolysis Activity in Platelets(Thromboembolism/Antithrombotic therapy/Thrombolysis-3, The 71st Annual Scientific Meeting of the Japanese Cir
- OE-010 GTP-induced Dense Granule Secretion in Platelets is Mediated by Ral GTPase-Exocyst Pathway(Molecular biology, vascular-1, The 71st Annual Scientific Meeting of the Japanese Circulation Society)
- 5 Noninvasive Risk Stratification of Subjects with a Brugada-Type Electrocardiogram and No Past History of Cardiac Arrest(Brugada Syndrome:From Cell to Bedside,Plenary Session 2 (PL2) (A),The 70th Anniversary Annual Scientific Meeting of the Japanese Circ
- PE-031 Predictive Value of Microvolt T-Wave Alternans for Sudden Cardiac Death in Patients with Preserved Cardiac Function after Acute Myocardial Infarction(Arrhythmia, diagnosis/pathophysiology/EPS-06, The 71st Annual Scientific Meeting of the Japanese C
- Predictive value of microvolt T-wave alternans for sudden cardiac death in patients with preserved cardiac function after acute myocardial infarction : Results of a collaborative cohort study
- PE-141 Effects of Amiodarone and Bepridil, Multi-channel Blockers, on Spiral Wave Reentries in Human Atrial Model with Electrical and Structural Remodelings(Arrhythmia, therapy(07)(A),Poster Session(English),The 72nd Annual Scientific Meeting of the Japan
- OE-383 Electrode Potential is Available for Evaluating the Local Repolarization during Fibrillation(ECG/Body surface potential mapping/Holter-1, The 71st Annual Scientific Meeting of the Japanese Circulation Society)
- Amiodarone Organizes Multiple Wavelets into Simple Spiral Reentry-by New Protocol for Automatically Visualizing Activation Propagation from "Electrode Mapping"(Arrhythmia, Pharmacological Therapy 4 (A), The 69th Annual Scientific Meeting of the Japanese C
- Clinical Usefulness of the Combination of T-Wave Alternans and Late Potentials for Identifying High-Risk Patients With Moderately or Severely Impaired Left Ventricular Function
- Combined assessment of T-wave alternans and late potentials used to predict arrhythmic events after myocardial infarction : A prospective study
- Resuscitation from Out-of-Hospital Cardiac Arrest Using External Defibrillators by Emergency Medical Service Staffs in Japan : A Single Medical Center Study(Arrhythmia, Non-pharmacological Therapy 8 (A), The 69th Annual Scientific Meeting of the Japanese
- Prevalence of Brugada-Type Electrocardiograms with Class IC Antiarrhythmic Drugs in Patients with Paroxysmal Atrial Tachyarrhythmias but no Risk-Stratifying Factors(ECG/Body Surface Potential Mapping/Holter 2 (A), The 69th Annual Scientific Meeting of the
- Risk Management Using Microvolt T-Wave Alternans Testing in Patients with Impaired Left Ventricular Function(Sudden Cardiac Death : Current Status and Preventive Measures, The 69th Annual Scientific Meeting of the Japanese Circulation Society)
- PJ-215 Antiarrhythmic efficacy of nifekalant to rescue from life-threatening polymorphic ventricular tachycardia/ventricular fibrillation associated with acute myocardial ischemia(Arrhythmia, Pharmacological Therapy 3 (A) : PJ36)(Poster Session (Japanese)
- Biatrial Pacing for Paroxysmal Atrial Fibrillation : The Outcome and Electrophysiological Mechanism of Prevention
- Prevention of Atrial Fibrillation using an Implantable Pacemaker : Crossover Trial between Bi-Atrial and Conventinal Right Atrial Pacing
- Comparison of Various Prognostic Valuables Including T-Wave Alternans in Predicting Arrhythmic Events During Long-Term Follow-up After Myocardial Infarction
- Evaluation of Bi-Atrial Pacing and Single Site Right Atrial Pacing for the Prevention of Atrial Fibrillation
- Atrial Double Potentials Associated With the Elimination of the Electrical Connection Between the Coronary Sinus (CS) and the Left Atrium in Two Cases of Wolff-Parkinson-White Syndrome With a CS-Connected Accessory Pathway
- PJ-294 Clinical Significance of the Admission Electrocardiogram QRS Duration in Acute Myocardial Infarction(Acute myocardial infarction, clinical (diagnosis/treatment)-8 (IHD) PJ50,Poster Session (Japanese),The 70th Anniversary Annual Scientific Meeting o
- OJ-378 Beat-to-beat Variation of T Waves "T-Wave Modulation" as a Harbinger of Cardiac Rupture after Acute Myocardial Infarction(ECG/Body surface potential mapping/Holter-3 (A) OJ63,Oral Presentation (Japanese),The 70th Anniversary Annual Scientific Meeti
- OJ-430 A New Strategy in Predicting Serious Cardiac Events After Acute Myocardial Infarction Using Time Course of a Filtered QRD Duration(ECG/Body Surface Potential Mapping/Holter 6 (A) : OJ52)(Oral Presentation (Japanese))
- PE-027 Relevance of J Wave in the Inferior and/or Left Lateral Leads in Patients with Syncope and no Apparent Heart Disease(Arrhythmia, diagnosis/pathophysiology/EPS-7 (A) PE5,Poster Session (English),The 70th Anniversary Annual Scientific Meeting of the
- PE-361 Useful Noninvasive Strategy to Detect Life-Threatening Events in Subjects with the Brugada-type Electrocardiogram : A Prospective Study(ECG/Body Surface Potential Mapping/Holler 7 (A) : PE62)(Poster Session (English))
- QT Dispersion as a Predictor for Subsequent Cardiac Events After Rotational Atherectomy : A Prospective study
- 2 Effects of Antiarrhythmic Drugs on Electrophysiological Action and Wavefront Dynamics During Atrial Fibrillation(Plenary Session 3 (PL3) (A) : Atrial Fibrillation : From bench to bedside)(Special Program)
- Statement for the Optimal Use of Home Electrocardiography 2007
- Circadian Variation in Out-of-Hospital Cardiac Arrests due to Cardiac Cause in a Japanese Patient Population
- Preparation of Organoytterbium Reagent from Ytterbium Trichloride and Organomagnesium
- Rotational Atherectomy Increases QT Dispersion Compared with Mere Stent Implantation
- The Refractory Gradient Increases the Incidence of VT/VF Induced by Sodium Channel Blockers
- Conversion of Multiple Non-Stationary Wavefronts to a Single Stationary Reentrant Wavefront by a Pure Ikr Channel Blocker in Canine Atria
- Noninvasive Strategies in Identifying Patients at Risk for Life-Threatening Arrhythmic Events
- Afterdepolarizations Promote the Transition From Ventricular Tachycardia to Fibrillation in a Three-Dimensional Model of Cardiac Tissue
- Differences in the R on T Phenomena Degenerating into VT/NF by between PVC and Catheter Pacing : A Simulation Study
- Transmural Dispersion of Repolarization Determines Scroll Wave Behavior During Ventricular Tachyarrhythmias : A Simulation Study
- Guidelines for Risks and Prevention of Sudden Cardiac Death (JCS 2010) : Digest Version
- Assessment of Relationship between Heart Rate Turbulence Parameters and Hemodynamic Indices in Patients with Pulmonary Hypertension
- An Overview of Current Strategies of Risk Assessment for Sudden Cardiac Death
- Risk Stratification and Pharmacological Management in Patients with Idiopathic Ventricular Fibrillation
- A Case of Breast Cancer with Chemotherapy-Induced Arrhythmias and No Cardiac Dysfunction by Trastuzumab, a Highly Effective Anticancer Agent
- Coronary Computed Tomography Angiography-Based Coronary Risk Stratification in Subjects Presenting With No or Atypical Symptoms
- Effects of Age and Gender on Heart Rate Turbulence in Healthy Population
- No Circadian Changes of Heart Rate Turbulence Parameters in Patients with Myocardial Infarction
- Optimal Dual-Chamber Pacing Therapy Improves Cardiac Function in a Patient with Complex Congenital Heart Disease and Bradyarrhythmias
- Current Status of Rate Control for Clinical Management of Patients with Atrial Fibrillation
- Simultaneous Assessment of T-Wave Alternans and Heart Rate Turbulence on Holter Electrocardiograms as Predictors for Serious Cardiac Events in Patients After Myocardial Infarction
- Selective Site Pacing From the Right Ventricular Mid-Septum : Follow-up of Lead Performance and Procedure Technique
- Irregular wide QRS complex tachycardia without structural heart disease
- Pharmacological Assessment in Young Patients with J-Wave Variation and Idiopathic Ventricular Fibrillation
- Effect on Cardiac Function of the Right Ventricular Mid-Septal Pacing Procedure with Narrow QRS Complexes in Patients with Permanent Pacemaker Implantation
- High Incidence of Inappropriate ICD Therapies in Young Patients with Catecholaminergic Polymorphic Ventricular Tachycardia