A5103053441- Lung Cancer Treatments and Mutations
- Marine Toxins and Detection Methods
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Lung Cancer Diagnosis and Treatment
- Cardiac electrophysiology and arrhythmias
- Catalysis and Hydrodesulfurization Studies
- Cell Adhesion Molecules Research
- Pancreatic and Hepatic Oncology Research
- PI3K/AKT/mTOR signaling in cancer
- Cancer Immunotherapy and Biomarkers
- Virus-based gene therapy research
- Cardiac Ischemia and Reperfusion
- Lung Cancer Research Studies
- Urinary Tract Infections Management
- Coal and Coke Industries Research
- Adipose Tissue and Metabolism
- Cardiomyopathy and Myosin Studies
- CRISPR and Genetic Engineering
- Metabolism, Diabetes, and Cancer
- Colorectal Cancer Treatments and Studies
- Viral Infections and Immunology Research
- Hepatocellular Carcinoma Treatment and Prognosis
- Ferroptosis and cancer prognosis
- RNA Interference and Gene Delivery
- Catalytic Processes in Materials Science
Teikyo Heisei University
2025
Seirei Mikatabara General Hospital
2016-2025
University of Tsukuba
2023-2025
Kobe Gakuin University
1995-2025
Toho University Ohashi Medical Center
2011-2024
Sapporo Kosei General Hospital
2024
Toho University
2011-2024
Kyushu Institute of Technology
2024
RIKEN Nishina Center
2024
Tohoku University
2024
The serine-threonine kinase Akt is activated by several ligand-receptor systems previously shown to be cardioprotective. activation reduces cardiomyocyte apoptosis in models of transient ischemia. Its role cardiac dysfunction or infarction, however, remains unclear.We examined the effects a constitutively active mutant (myr-Akt) rat model ischemia-reperfusion injury. In vivo gene transfer myr-Akt reduced infarct size 64% and number apoptotic cells 84% (P<0.005 for each). Ischemia-reperfusion...
A soluble extract prepared from human cells (KB S-100) has been recently shown to direct accurate transcription initiation by purified RNA polymerase II at the major late promoter of adenovirus 2. We have fractionated this chromatography on phosphocellulose, DEAE-cellulose, and DNA-cellulose, identified four components that are required for active selective promoter. One these seems act suppressing random, but not selective, II. All one be chromatographically distinct factors involved in...
In human and experimental models of heart failure, sarcoplasmic reticulum Ca 2+ ATPase (SERCA2a) activity is decreased, resulting in abnormal calcium handling. The disturbances metabolism have been shown to contribute significantly the contractile dysfunction observed failure. We investigated whether increasing SERCA2a expression can improve ventricular function an animal model failure obtained by creating ascending aortic constriction rats. After 19–23 wk banding during transition from...
Background —Failing human myocardium is characterized by abnormal relaxation, a deficient sarcoplasmic reticulum (SR) Ca 2+ uptake, and negative frequency response, which have all been related to deficiency in the SR ATPase (SERCA2a) pump. Methods Results —To test hypothesis that an increase SERCA2a could improve contractile function cardiomyocytes, we overexpressed ventricular myocytes from 10 patients with end-stage heart failure examined intracellular handling function. Overexpression of...
The serine-threonine kinase, Akt, inhibits cardiomyocyte apoptosis acutely both <i>in vitro</i> and vivo</i>. However, the effects of chronic Akt activation in heart are unknown. To address this issue, we generated transgenic mice (TG+) with cardiac-specific expression a constitutively active mutant (myr-Akt) driven by myosin heavy chain-α promoter. Three TG+ founders (9–19 weeks) died suddenly massive cardiac dilatation. Two viable lines (TG564 TG20) derived from independent demonstrated...
Cell-free extracts (5-100) prepared from cultured mammalian KB cells have previously been shown to direct accurate and selective transcription of class 111 genes by RNA polymerase III.We fractionated the S-100 found that multiple components are essential for these genes.After has separated into four different protein fractions chromatography on phosphocellulose, two required, in addition III, active virus-associated RNA1 gene adenovirus 2 a tRNA gene; third fraction is along with components,...
Clinical studies have suggested that myocardial iron is a risk factor for left ventricular remodeling in patients after infarction. Ferroptosis has recently been reported as mechanism of iron-dependent nonapoptotic cell death. However, ferroptosis the heart not well understood. Mechanistic target rapamycin (mTOR) protects against pathological stimuli such ischemia. To define role cardiac mTOR on survival iron-mediated death, we examined cardiomyocyte (CM) viability under excess and...
Hypertrophy is a basic cellular response to variety of stressors and growth factors, has been best characterized in myocytes. Pathologic hypertrophy cardiac myocytes leads heart failure, major cause death disability the developed world. Several cytosolic signaling pathways have identified that transduce prohypertrophic signals, but date, little work focused on might negatively regulate hypertrophy. Herein, we report glycogen synthase kinase-3β (GSK-3β), protein kinase previously implicated...
Background —The intracellular signaling pathways that control cardiomyocyte apoptosis have not been fully defined. Because insulin-like growth factor-1 (IGF-1) prevents apoptosis, we examined the role of its downstream molecules in an vitro model hypoxia-induced apoptosis. Methods and Results —Treatment rat neonatal cardiomyocytes with IGF-1 increased activity both phosphatidylinositol 3′ (PI 3)-kinase target, Akt (also known as protein kinase B or PKB). Cardiomyocytes were subjected to...
Inactivation of glycogen synthase kinase 3β (GSK3β) and the resulting stabilization free β-catenin are critical steps in activation Wnt target genes. While Akt regulates GSK3α/β phosphatidylinositide 3-OH signaling pathway, its role is unknown. Here we report that expression or Dishevelled (Dvl) increased activity. Activated bound to Axin-GSK3β complex presence Dvl, phosphorylated GSK3β levels. Furthermore, Wnt-overexpressing PC12 cells, dominant-negative decreased derepressed nerve growth...
We used a catheter-based technique to achieve generalized cardiac gene transfer in vivo and alter function by overexpressing phospholamban (PL) which regulates the activity of sarcoplasmic reticulum Ca2+ ATPase (SERCA2a). By using this approach, rat hearts were transduced with 5 x 10(9) pfu recombinant adenoviral vectors carrying cDNA for either PL, beta-galactosidase (beta-gal), or modified green fluorescent protein (EGFP). Western blot analysis ventricles obtained from rats Ad.PL showed...
Abstract The ability to image cardiomyocyte apoptosis in vivo with high‐resolution MRI could facilitate the development of novel cardioprotective therapies. sensitivity nanoparticle AnxCLIO‐Cy5.5 for was thus compared vitro that annexin V‐FITC and showed a high degree colocalization. then performed, following transient coronary artery (LAD) occlusion, five mice given four an identical dose (2 mg Fe/kg) CLIO‐Cy5.5. MR signal intensity myocardial T 2 * were evaluated, vivo, hypokinetic regions...
Acute activation of the serine-threonine kinase Akt is cardioprotective and reduces both infarction dysfunction after ischemia/reperfusion injury (IRI). However, less known about chronic effects in heart, and, paradoxically, activated samples from patients with heart failure. We generated Tg mice cardiac-specific expression either (myristoylated [myr]) or dominant-negative (dn) assessed their response to IRI an ex vivo model. While dn-Akt hearts demonstrated a moderate reduction functional...
Missense mutations in the 695-amino acid form of amyloid precursor protein (APP 695 ) cosegregate with disease phenotype families dominantly inherited Alzheimer's disease. These convert valine at position 642 to isoleucine, phenylalanine, or glycine. Expression these mutant proteins, but not normal APP , was shown induce nucleosomal DNA fragmentation neuronal cells. Induction required cytoplasmic domain mutants and appeared be mediated by heterotrimeric guanosine triphosphate-binding...
Akt activation reduces cardiomyocyte death and induces cardiac hypertrophy. To help identify effector mechanisms, gene expression profiles in hearts from transgenic mice with cardiac-specific of activated (myr-Akt) were compared littermate controls. 40 genes identified as differentially expressed. Quantitative reverse transcription-PCR confirmed qualitative results transcript profiling for 9 10 examined, however, there notable quantitative discrepancies between the microarray data sets....
Autoimmunity has long been linked to myocarditis and its sequela, dilated cardiomyopathy, the leading causes of heart failure in young patients. However, underlying mechanisms are poorly defined, with most clinical investigations focused on humoral autoimmunity as target for intervention. Here, we show that α-isoform myosin heavy chain (α-MyHC, which is encoded by gene Myh6) pathogenic autoantigen CD4+ T cells a spontaneous mouse model myocarditis. Further, found Myh6 transcripts were absent...
In many systems, activation of the “protein and lipid kinase” phosphoinositide 3-kinase (PI 3-kinase) its downstream serine-threonine kinase effector, Akt (or Protein Kinase B), provide a potent stimulus for cell proliferation, growth, survival. heart, constrained by limited proliferative capacity cardiomyocytes, this pathway plays key role in regulating cardiomyocyte growth survival, with little effect on proliferation. Simultaneously, PI are important modulators metabolic substrate...
Abstract The successive phase transitions of the polymorphs CsSnI3 were studied by means powder X-ray diffraction and their crystal structures analyzed at three different temperatures Rietveld method.
TFIIC is a factor found earlier in our laboratory to be required for eliminating random transcription by RNA polymerase I1 and thereby facilitating the detection of specific initiation on promoter-containing DNA templates presence other essential (class 11) factors (Matsui,