A5014423509- Cardiac Fibrosis and Remodeling
- Cytokine Signaling Pathways and Interactions
- Signaling Pathways in Disease
- Cardiac Ischemia and Reperfusion
- Viral Infections and Immunology Research
- Aldose Reductase and Taurine
- Cardiomyopathy and Myosin Studies
- Cell Adhesion Molecules Research
- Nitric Oxide and Endothelin Effects
- Eicosanoids and Hypertension Pharmacology
- Protein Tyrosine Phosphatases
- Receptor Mechanisms and Signaling
- Cardiovascular Function and Risk Factors
- Ion channel regulation and function
- RNA Research and Splicing
- Peroxisome Proliferator-Activated Receptors
- Angiogenesis and VEGF in Cancer
- PI3K/AKT/mTOR signaling in cancer
- Cardiac electrophysiology and arrhythmias
- Chronic Kidney Disease and Diabetes
- Peptidase Inhibition and Analysis
- Adipose Tissue and Metabolism
- Pharmacogenetics and Drug Metabolism
- Heart Failure Treatment and Management
- Tissue Engineering and Regenerative Medicine
Osaka University
2015-2024
Osaka Medical Center for Cancer and Cardiovascular Diseases
1993-2024
Osaka University of Pharmaceutical Sciences
2006-2023
Daiichi-Sankyo (Japan)
2017
Kumamoto University
2012
PharmacoGenetics (China)
2008-2012
The University of Tokyo
2011
Hyogo University of Health Sciences
2009-2010
Osaka Health Science University
2008
Molecular Oncology (United States)
2003
Background —IGF-1 has been shown to protect myocardium against death in animal models of infarct and ischemia-reperfusion injury. In the present study, we investigated role IGF-1–regulated protein kinase Akt cardiac myocyte survival vitro vivo. Methods Results promoted cultured cardiomyocytes under conditions serum deprivation a dose-dependent manner but had no effect on fibroblast survival. The cytoprotective IGF-1 was abrogated by phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor...
Angiotensin II, a hypertrophic/anti-apoptotic hormone, utilizes reactive oxygen species (ROS) as growth-related signaling molecules in vascular smooth muscle cells (VSMCs). Recently, the cell survival protein kinase Akt/protein B (PKB) was proposed to be involved synthesis. Here we show that angiotensin II causes rapid phosphorylation of Akt/PKB (6- ± 0.4-fold increase). Exogenous H2O2 (50–200 μm) also stimulates (maximal 8- 0.2-fold increase), suggesting activation is redox-sensitive. Both...
Regulation of endothelial cell apoptosis is a critical modulator normal and pathological angiogenesis. In this study, we examined the role protein kinase Akt/PKB in survival response to growth factor matrix attachment signals. Vascular factor(VEGF)-induced cytoprotection monolayers correlated with wortmannin-sensitive induction Akt activity. Transfection an adenovirus expressing dominant-negative mutant decreased viability presence VEGF. Conversely, adenoviral transduction wild-type...
Vascular endothelial growth factor (VEGF) induces cell proliferation, migration, and actin reorganization, all necessary components of an angiogenic response. However, the distinct signal transduction mechanisms leading to each phenotype are not known. In this study, we examined ability VEGF stimulate migration rearrangement in microvascular cells infected with adenoviruses encoding beta-galactosidase (beta-gal), activation-deficient Akt (AA-Akt), or constitutively active (myr-Akt)....
This study is a pharmacogenetic clinical trial designed to clarify whether the N-acetyltransferase 2 gene (NAT2) genotype-guided dosing of isoniazid improves tolerability and efficacy 6-month four-drug standard regimen for newly diagnosed pulmonary tuberculosis.In multicenter, parallel, randomized, controlled with PROBE design, patients were assigned either conventional treatment (STD-treatment: approx. 5 mg/kg all) or NAT2 (PGx-treatment: 7.5 homozygous 4: rapid acetylators; mg/kg,...
Background Mice with cardiac-specific overexpression of signal transducer and activator transcription 3 (STAT3) are resistant to doxorubicin-induced damage. The STAT3 may be involved in the detoxification reactive oxygen species (ROS). Methods Results effects leukemia inhibitory factor (LIF) or adenovirus-mediated transfection constitutively activated (caSTAT3) on intracellular ROS formation induced by hypoxia/reoxygenation (H/R) were examined using rat neonatal cardiomyocytes. Either LIF...
Background —gp130, a signal transducer of the IL-6–related cytokines, is expressed ubiquitously, including in heart. The activation gp130 cardiac myocytes was reported to induce myocardial hypertrophy. downstream side consists two distinct pathways myocytes, one Janus kinase/signal and activator transcription (JAK/STAT) pathway, other mitogen-activated protein kinase (MAPK) pathway. In present study, we examined whether JAK/STAT especially STAT3-mediated plays critical role gp130-dependent...
We recently reported that the activation of glycoprotein (gp) 130 by leukemia inhibitory factor (LIF) upregulates Bcl-xL and exerts antiapoptotic effects in cardiac myocytes. In addition, LIF induces phosphatidylinositol (PI) 3-kinase Akt, which are known to be required for cell survival. However, their regulatory roles death remain unknown.We investigated fate these proteins cytoprotective on doxorubicin (DOX)-induced apoptosis cultured neonatal rat Myocyte increased significantly...
Application of foreign clinical data across geographic regions can accelerate drug development. Drug disposition be variable, and identification factors influencing responsible pharmacokinetic/pharmacogenomic approaches could facilitate the universal application reduce total amount phase III trials evaluating risks in different populations. Our objective was to establish compare genotype (major cytochrome P450 (CYP) enzymes)/phenotype associations for Japanese (native first- third-generation...
During myogenesis, proliferating myoblasts withdraw from the cell cycle, acquire an apoptosis-resistant phenotype, and differentiate into myotubes. Previous studies indicate that myogenic induction of cyclin-dependent kinase inhibitor p21 results in inhibition apoptotic death addition to its role as a negative cycle regulator. Here we demonstrate protein encoded by Akt proto-oncogene is induced C2C12 cells during differentiation with corresponding increase activity. In differentiating...
Phosphatidylinositol (PI) 3-kinase is known to be activated by cytokine stimulation through different types of receptors transduce intracellular responses. We have previously reported that leukemia inhibitory factor (LIF) induces the activation Janus kinase signal transducer and activator transcription (JAK-STAT) mitogen-activated protein (MAP) pathways glycoprotein (gp) 130 in cardiac myocytes. However, whether PI involved regulation gp130 signaling mechanisms which it associates with other...
The serine/threonine protein kinase Akt (protein B) phosphorylates endothelial cell nitric oxide synthase (eNOS) and enhances its ability to generate (NO). Because NO is an important regulator of vasomotor tone, we investigated whether can regulate endothelium-dependent vasomotion in vivo using a rabbit femoral artery model gene transfer. endothelium isolated arteries was infected with replication-defective adenoviral constructs expressing β-galactosidase, constitutively-active (myr-Akt), or...
We described recently the activation of Janus kinasesignal transducer and activator transcription (JakSTAT) mitogen-activated protein (MAP) kinase pathways by leukemia inhibitory factor (LIF) through gp130, a signal IL-6-related cytokines, that transduces hypertrophic signals in cardiac myocytes. In addition, stimulation gp130 cytokines is known to exert cytoprotective effect. present study, we investigated possibility initiates genes Incubation myocytes with LIF induced expression bcl-x,...
Background Interleukin (IL)-6–related cytokines share gp130 as the signal-transducing protein. Downstream of gp130, two pathways have been recognized, Janus kinase–signal transducer and activator transcription (JAK-STAT) pathway Ras–mitogen-activated protein kinase (MAPK) pathway. To determine whether these signaling through are present in cardiac myocytes, we examined their activation by using leukemia inhibitory factor (LIF), which is a member IL-6 cytokine family. Methods Results Lysates...
Background— Glycoprotein 130 is the common receptor subunit for interleukin (IL)-6 cytokine family. Previously, we reported that pretreatment of IL-11, an IL-6 family cytokine, activates glycoprotein signaling pathway in cardiomyocytes and prevents ischemia/reperfusion injury vivo; however, its long-term effects on cardiac remodeling after myocardial infarction (MI) remain to be elucidated. Methods Results— MI was generated by ligating left coronary artery C57BL/6 mice. Real-time reverse...
In the initial process of coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome 2 (SARS-CoV-2) infects epithelial cells and then transfers to other organs blood vessels. It is believed that SARS-CoV-2 can pass vascular wall by altering endothelial barrier using an unknown mechanism. this study, we investigated effect on airway-on-a-chip mimics found produced from infected disrupts decreasing Claudin-5 (CLDN5), a tight junction protein, disrupting cadherin–mediated adherens...
Objective: Activation of signal transducer and activator transcription 3 (STAT3) was reported to be correlated with myocardial protection against ischemia/reperfusion (I/R) injury in ischemic preconditioning. Here, we tested the causality between STAT3 activity cardioprotection. We also addressed molecular mechanism for its
Activation of glycoprotein (gp) 130 transduces hypertrophic and cytoprotective signals in cardiac myocytes. In the present study, we have demonstrated that through gp130 increase expression vascular endothelial growth factor (VEGF) myocytes via signal transducer activator transcription (STAT) 3 pathway. After activation with leukemia inhibitory (LIF), VEGF mRNA rapidly increased a peak at h cultured Cardiotrophin-1 also enhanced dose-dependent manner. protein production secretion to medium...