A5015624012- Cardiac Ischemia and Reperfusion
- Mitochondrial Function and Pathology
- Cardiovascular Function and Risk Factors
- Sirtuins and Resveratrol in Medicine
- Cardiac electrophysiology and arrhythmias
- Electrolyte and hormonal disorders
- Cell death mechanisms and regulation
- Autophagy in Disease and Therapy
- Renin-Angiotensin System Studies
- Diabetes Treatment and Management
- Adipose Tissue and Metabolism
- Hormonal Regulation and Hypertension
- Erythropoietin and Anemia Treatment
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Acute Kidney Injury Research
- Pancreatic function and diabetes
- Cardiac Fibrosis and Remodeling
- ATP Synthase and ATPases Research
- Anesthesia and Neurotoxicity Research
- Connexins and lens biology
- Fuel Cells and Related Materials
- Metabolism, Diabetes, and Cancer
- Receptor Mechanisms and Signaling
- Cardiac Arrest and Resuscitation
- Metabolism and Genetic Disorders
Sapporo Medical University
2015-2024
Sapporo Science Center
2017
Sapporo University
2007-2016
King's College London
2003-2009
Chonnam National University
2009
Chonnam National University Hospital
2009
St Thomas' Hospital
2003-2006
Yale University
2003
Howard Hughes Medical Institute
2003
National Hospital Organization Hanamaki Hospital
1990-1991
Sir2 (silent information regulator 2) is an NAD+-dependent histone deacetylase that contributes to longevity in yeast. SIRT1, a mammalian ortholog, deacetylates histones and various transcription factors, including p53, FOXO proteins, peroxisome proliferator-activated receptor-γ. We found its subcellular localization varied different tissues of the adult mouse. Some subsets neurons predominantly expressed SIRT1 cytoplasm, but ependymal cells it both nucleus cytoplasm. On other hand,...
Oxidative stress plays a pivotal role in chronic heart failure. SIRT1, an NAD+-dependent histone/protein deacetylase, promotes cell survival under oxidative when it is expressed the nucleus. However, adult cardiomyocytes predominantly express SIRT1 cytoplasm, and its function has not been elucidated. The purpose of this study was to investigate functional potential use therapy for We investigated subcellular localization impact on survival. accumulated nucleus failing hearts TO-2 hamsters,...
Neural precursor cells (NPCs) differentiate into neurons, astrocytes, and oligodendrocytes in response to intrinsic extrinsic changes. Notch signals maintain undifferentiated NPCs, but the mechanisms underlying neuronal differentiation are largely unknown. We show that SIRT1, an NAD(+)-dependent histone deacetylase, modulates differentiation. SIRT1 was found cytoplasm of embryonic adult NPCs transiently localized nucleus stimulus. started translocate within 10 min after transfer conditions,...
Muscular dystrophies are inherited myogenic disorders accompanied by progressive skeletal muscle weakness and degeneration. We previously showed that resveratrol (3,5,4′-trihydroxy-<i>trans</i>-stilbene), an antioxidant activator of the NAD<sup>+</sup>-dependent protein deacetylase SIRT1, delays progression heart failure prolongs lifespan δ-sarcoglycan-deficient hamsters. Because a defect dystroglycan complex causes muscular dystrophies, δ-sarcoglycan is component this complex, we...
To explore mechanisms by which SGLT2 inhibitors protect diabetic hearts from heart failure, we examined the effect of empagliflozin (Empa) on ultrastructure cardiomyocytes in noninfarcted region after myocardial infarction (MI). OLETF, a rat model type 2 diabetes, and its nondiabetic control, LETO, received sham operation or left coronary artery ligation 12 h before tissue sampling. Tissues were sampled posterior ventricle (i.e., remote rats with MI). The number mitochondria was larger small...
The mechanism by which SGLT2 inhibitors reduce cardiac events in diabetic patients remains unclear. Here, we examined the effects of an inhibitor on acute survival rate after myocardial infarction (MI) animal model type 2 diabetes mellitus (DM) and possible involvement modification metabolomes antioxidative proteins. MI was induced DM Otsuka Long-Evans Tokushima Fatty (OLETF) rats (LETO) control rats. Treatment with empagliflozin (10 mg/kg per day, 14 days) before reduced blood glucose...
We examined whether the mitochondrial ATP-sensitive K channel (K(ATP)) is an effector downstream of protein kinase C-epsilon (PKC-epsilon) in mechanism preconditioning (PC) isolated rabbit hearts. PC with two cycles 5-min ischemia/5-min reperfusion before 30-min global ischemia reduced infarction from 50.3 +/- 6.8% left ventricle to 20.3 3.7%. significantly increased PKC-epsilon particulate fraction 51 4% total 60 4%, whereas no translocation was observed for PKC-delta and PKC-alpha. In...
The ischemic activation of p38α mitogen-activated protein kinase (p38α-MAPK) is thought to contribute myocardial injury. Under other circumstances, through dual phosphorylation by MAPK 3 (MKK3). Therefore, the mkk3 −/− murine heart should be protected during ischemia. In retrogradely perfused and +/+ mouse hearts subjected 30 minutes global ischemia 120 reperfusion, infarction/risk volume was similar (50±5 versus 51±4, P =0.93, respectively), as intraischemic p38-MAPK (10 percent basal,...
The aim of this study was to determine whether erythropoietin (EPO) affords additional cardioprotection the preconditioned myocardium by enhanced phosphorylation Akt, STAT3, or glycogen synthase kinase-3beta (GSK-3 beta). Preconditioning (PC) with 5-min ischemia/5-min reperfusion and EPO (5,000 U/kg iv) reduced infarct size (as % area at risk, %IS/AR) after 20-min ischemia in rat hearts situ from 56.5 +/- 1.8% 25.2 2.1% 36.2 2.8%, respectively. PC-induced protection significantly inhibited a...
OBJECTIVE Alteration in endoplasmic reticulum (ER) stress diabetic hearts and its effect on cytoprotective signaling are unclear. Here, we examine the hypothesis that ER impairs phospho–glycogen synthase kinase (GSK)-3β–mediated suppression of mitochondrial permeability transition pore (mPTP) opening, compromising myocardial response to signaling. RESEARCH DESIGN AND METHODS A rat model type 2 diabetes (OLETF) control (LETO) were treated with tauroursodeoxycholic acid (TUDCA) (100 mg · kg−1...
The mitochondrial permeability transition pore (mPTP) is a non-selective, large-conductance channel that closed under physiological conditions. Opening of the mPTP, leading to abolition functions, major mechanism myocyte necrosis by ischaemia/reperfusion, and direct inhibition mPTP opening use pharmacological or genetic manipulations limits infarct size in vivo. Multiple pro-survival signal pathways commonly target inhibit its opening. Although molecular structure has not been established,...
Glycogen synthase kinase-3β (GSK-3β) is a major positive regulator of the mitochondrial permeability transition pore (mPTP), principle trigger cell death, under condition oxidative stress. However, mechanism by which cytosolic GSK-3β translocates to mitochondria, promoting mPTP opening, remains unclear. Here we addressed this issue analyses effect site-directed mutations in on translocation and protein/protein interactions upon H9c2 cardiomyoblasts were transfected with GFP-tagged (WT),...
Fulminant myocarditis presentation (FMP) is a rare and severe of myocarditis. The natural history FMP its clinical features associated with poor outcomes are incompletely understood because there lack generalizable evidence.This multicenter retrospective cohort study included patients hospitalized histologically proven who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 March 2017. Clinical the prognostic predictors...
SIRT1, a NAD(+)-dependent protein deacetylase, is known to have neural functions. However, despite its cytoplasmic expression in some cells, function, if any, unknown. Here we found that PC12 (pheochromocytoma) cells expressed SIRT1 the cytoplasm. Nerve growth factor (NGF)-induced neurite outgrowth of these was promoted by activators while inhibitors or SIRT1-siRNA significantly inhibited it. The overexpression mutant localised cytoplasm but not nucleus enhanced NGF-dependent outgrowth, and...
Diabetes mellitus (DM) is associated with an increased risk of ischemic heart disease and adverse outcomes following myocardial infarction (MI). Here we assessed the role endoplasmic reticulum (ER) stress in ventricular dysfunction after MI type 2 DM (T2DM).In hearts OLETF, a rat model T2DM, at 25∼30 weeks age, GRP78 GRP94, markers ER stress, were sarcoplasmic calcium ATPase (SERCA)2a protein was reduced by 35% compared those LETO, non-diabetic control. SERCA2a mRNA levels similar, but more...
Type 2 diabetes mellitus (T2DM) worsens the outcome after myocardial infarction (MI). Here, we hypothesized that inhibition of dipeptidyl peptidase-4 (DPP-4) improves survival MI in T2DM by modifying autophagy non-infarcted region heart. Under baseline conditions, there was no significant difference between levels marker proteins OLETF, a rat model T2DM, and LETO, non-diabetic control. However, contrast to response LC3-II protein LC3-positive autophagosomes myocardium were not increased...
Type 2 diabetes mellitus is a risk factor of acute kidney injury after myocardial infarction (MI), form cardiorenal syndrome. Recent clinical trials have shown that sodium-glucose cotransporter (SGLT2) inhibitor improved both cardiac and renal outcomes in patients with type mellitus, but effects an SGLT2 on syndrome remain unclear.Type (Otsuka Long-Evans Tokushima Fatty rats [OLETF]) control (Long-Evans Otsuka [LETO]) were treated canagliflozin, inhibitor, for weeks. Renal tissues analyzed...
Accumulating evidence indicates that necroptosis contributes to cardiovascular diseases. We recently reported suppression of autophagy by necroptotic signals in cardiomyocytes and protective action rapamycin. Here we examined the mechanism which mTORC1 inhibition protects from necroptosis. Necroptosis H9c2 cells was induced treatment with tumor necrotic factor-α (TNF) z-VAD-fmk (zVAD), extent determined as level LDH release (as % total). TNF/zVAD increased RIP1-RIP3 interaction 3.4 ± 1.3%...
The aim of the present study was to examine hypothesis that acceleration gap junction (GJ) closure during ischemia contributes anti-infarct tolerance afforded by preconditioning (PC). First, effects PC on GJ communication were assessed. Isolated buffer-perfused rabbit hearts subjected 5-min global with or without two cycles ischemia/5-min reperfusion a blocker (2 mM heptanol), and then tissue excised from ischemic region incubated in anoxic buffer containing lucifer yellow (LY; 2.5 mg/ml),...
The aim of this study was to determine the role GSK-3β in cardiomyocyte protection afforded by erythropoietin (EPO) against oxidant stress-induced apoptosis. Treatment with EPO (10 units/ml) induced Ser473 phosphorylation Akt and Ser9 significantly reduced proportion apoptotic H9c2 cardiomyocytes after exposure H 2 O from 38.3 ± 2.7% 26.0 2.9%. This not detected cells transfected constitutively active (S9A), which lacks for inhibitory phosphorylation. antiapoptotic effect mimicked completely...