A5064755201- Mitochondrial Function and Pathology
- Virus-based gene therapy research
- Receptor Mechanisms and Signaling
- Liver physiology and pathology
- ATP Synthase and ATPases Research
- CAR-T cell therapy research
- Genetic and Kidney Cyst Diseases
- Calcium signaling and nucleotide metabolism
- RNA Interference and Gene Delivery
- Autophagy in Disease and Therapy
- Protein Kinase Regulation and GTPase Signaling
- Organ Transplantation Techniques and Outcomes
- Wnt/β-catenin signaling in development and cancer
- Diabetes Treatment and Management
- Mast cells and histamine
- Chemotherapy-induced cardiotoxicity and mitigation
- Neuropeptides and Animal Physiology
- Viral Infectious Diseases and Gene Expression in Insects
- CRISPR and Genetic Engineering
- Peptidase Inhibition and Analysis
- Liver Disease Diagnosis and Treatment
- PI3K/AKT/mTOR signaling in cancer
- Helicobacter pylori-related gastroenterology studies
- Pancreatic function and diabetes
- Biochemical effects in animals
Tohoku University
2012-2023
Akita University
2000-2020
Tohoku Fukushi University
2019
Shokei Gakuin University
2019
Laboratory of Molecular Genetics
2015
Ontario Institute for Cancer Research
2005-2009
Nippon Flour Mills (Japan)
1992-2006
University Health Network
2004-2005
University of Toronto
2004
Hospital for Sick Children
2004
See page 848Gene therapy and stem cell transplantation safety could be enhanced by control over the fate of therapeutic cells. Suicide gene uses enzymes that convert prodrugs to cytotoxic entities; however, heterologous moieties with poor kinetics are employed. We describe a novel enzyme/prodrug combination for selectively inducing apoptosis in lentiviral vector–transduced Rationally designed variants human thymidylate kinase (tmpk) effectively phosphorylate 3′-azido-3′-deoxythymidine (AZT)...
Mitochondrial dysfunction causes increased oxidative stress and depletion of ATP, which are involved in the etiology a variety renal diseases, such as CKD, AKI, steroid–resistant nephrotic syndrome. Antioxidant therapies being investigated, but clinical outcomes have yet to be determined. Recently, we reported that newly synthesized indole derivative, mitochonic acid 5 (MA-5), increases cellular ATP level survival fibroblasts from patients with mitochondrial disease. MA-5 modulates synthesis...
Mitochondrial dysfunction increases oxidative stress and depletes ATP in a variety of disorders. Several antioxidant therapies drugs affecting mitochondrial biogenesis are undergoing investigation, although not all them have demonstrated favorable effects the clinic. We recently reported therapeutic drug mitochonic acid MA-5 (Tohoku J. Exp. Med., 2015). increased ATP, rescued disease fibroblasts prolonged life span model "Mitomouse" (JASN, 2016). To investigate potential on various diseases,...
Successful therapy for many inherited disorders could be improved if the intervention were initiated early. This is especially true lysosomal storage disorders. Earlier may allow metabolic correction to occur before lipid buildup has irreversible consequences and/or immune system mounts limiting responses. We have been developing gene treat disorders, Fabry disease. describe studies directed toward in neonatal animals mediated by recombinant lentiviral vectors. To develop this method, we...
Our study reports a preliminary investigation into the role of human H2 relaxin in prostate tumor growth. A luciferase-expressing cancer cell line, PC-3, was generated and termed PC3-Luc. PC3-Luc cells were transduced with lentiviral vectors engineering expression either enhanced green fluorescent protein (eGFP) or both eGFP bicistronic format. These PC3-Luc-eGFP PC3-Luc-H2/eGFP, respectively. To gauge effects, PC3-Luc-H2/eGFP injected NOD/SCID mice monitored over 6 weeks. PC-3 xenografts...
Mitochondria are key organelles implicated in a variety of processes related to energy and free radical generation, the regulation apoptosis, various signaling pathways. Mitochondrial dysfunction increases cellular oxidative stress depletes ATP inherited mitochondrial diseases also many other metabolic neurodegenerative diseases. characterized by respiratory chain, caused mutations genes encoded either nuclear DNA or DNA. We have hypothesized that chemicals increase levels may ameliorate...
Doxorubicin (Dox), an anthracycline antibiotic, is anticancer drug that inhibits DNA replication and cellular metabolic processes in cancer cells with high proliferative potential. However, Dox causes severe side effects, including myocardial damage heart failure, but the molecular mechanism underlying Dox-induced injury remains uncertain. In present study, we evaluated effects of on mitochondrial quality control system regulation respiration autophagy vitro rat myoblast H9c2 cell culture...
Introduction: Moyamoya disease (MMD) is a cerebrovascular characterized by progressive steno-occlusive lesions in the terminal portion of internal carotid artery. Despite its unknown etiology, immune dysregulation regarded as critical trigger for delineating pathophysiology MMD. The gut microbiota produces short-chain fatty (SCFA) and organic acids, influencing regulation vascular remodeling. We aimed to characterize patients with Methods: Sixteen MMD sixteen healthy controls were included...
SUMMARY Emerging evidence strongly supports a close relationship between age-related hearing loss and frailty, highlighting the importance of early detection intervention. Recently, we invented mitochondria-homing drug named mitochonic acid 5 (MA-5), that increases adenosine triphosphate (ATP) levels, rescue mitochondrial function, protect tissue damages. Currently, phase I clinical trial has been finished in Japan (jRCT2031210495) 2 already approved by PMDA. Here show MA-5 improved various...
We previously described a novel suicide (or 'cell fate control') gene therapy enzyme/prodrug system based on an engineered variant of human thymidylate kinase (TMPK) that potentiates azidothymidine (AZT) activation. Delivery sequence into tumors by lentiviral transduction embodies cancer could employ bystander cell killing as mechanism driving significant tumor regression in vivo. Here we present evidence vitro and vivo mediated the TMPK/AZT axis is reliant formation functional...
To elucidate a role of costimulatory molecule and cell adhesion in hepatic ischemia/reperfusion injury, we examined an alteration B7-1 (CD80), B7-2 (CD86), intercellular 1 (ICAM-1; CD54) expression the rat liver after warm injury. induce ischemia model, both portal vein artery entering left-lateral median lobes were occluded by clamping for 30 minutes or 60 minutes, then reperfused 24 hours. B7-1, B7-2, ICAM-1 expressions analyzed immunofluorescence staining real-time reverse transcription...
The safety of cell therapy applications can be enhanced by the introduction Cell Fate Control (CFC) elements, which encode pharmacologically controlled cellular suicide switches. CFC Gene Therapy (CFCGT) offers possibility establishing control over gene-modified cells (GMCs) with regards to their proliferation, differentiation, or function. However, enzymes commonly employed in these approaches often possess poor kinetics and high immunogenicity. We describe a novel CFCGT system based on...
Highly active anti-retrovirus therapy (HAART) has been used to block the progression and symptoms of human immunodeficiency virus infection. Although it decreases morbidity mortality, clinical use HAART also linked various adverse effects such as severe cardiomyopathy resulting from compromised mitochondrial functioning. However, mechanistic basis for these remains unclear. Here, we demonstrate that a key component HAART, 3ꞌ-azido-3ꞌ-deoxythymidine (AZT), particularly, its metabolite...
The anti-inflammatory effects of macrolides may be associated with a reduced frequency exacerbation chronic obstructive pulmonary disease (COPD). However, because the long-term use antibiotics promote growth drug-resistant bacteria, development treatment to prevent COPD that do not exert anti-bacterial is necessary. Additionally, inhibitory nonantibiotic on replication rhinovirus (RV), which major cause exacerbation, have been demonstrated. Primary cultures human tracheal epithelial cells...
LEC rats spontaneously develop hepatocellular carcinoma with cholangiofibrosis after chronic hepatitis, but the mechanism of development hepatic injury is not clear. To investigate role stellate cells in induction or suppression fibrosis, we morphologically examined liver rats. Accumulation copper was analyzed by Danscher-Timm's sulfide-silver method. Histopathological changes were evaluated hematoxylin and eosin staining, Masson's trichrome Activated identified immunostaining method for...
A specific binding of the cholecystokinin (CCK)-releasing peptide (monitor peptide) to isolated rat jejunal mucosal cells was investigated. The 125I-labelled purified monitor bound cells, and a large excess amount non-labelled inhibited binding. completed within 60 min at 37 degrees C. optimum pH for 8-9. Scatchard plot linear, dissociation constant 50 nM. density monitor-peptide-binding sites high in duodenum but low ileal absent colonic mucosa. recombinant four kinds point mutants it were...
The selectivities, potencies and efficacies of β3-adrenoceptor (β3-AR) agonists on human three β-AR subtypes expressed in Chinese hamster ovary (CHO) cells were investigated using radioligand binding assay cyclic AMP (cAMP) accumulation assay. showed the nature G protein-coupled receptors with constitutive activity. BRL37344, CL-316, 243 a newly synthesized β3-AR agonist N-5984, 6-[2-(R)-[[2-(R)-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-2, 3-dihydro-1, 4-benzodioxine-2-(R)-carboxylic...
A gene coding for yeast 15‐kDa protein, a regulatory factor of mitochondrial F 1 0 ‐ATPase, was isolated. The cloned disrupted in vitro and mutant strains that did not contain the protein were constructed by transformation cells with gene. ATP‐synthesizing activity mitochondria same as wild‐type cells, suggesting is required oxidative phosphorylation. Collapse membrane potential induced ATP‐hydrolyzing ‐ATPase but normal mitochondria. Activation enzyme also observed during incubation...
We examined the effects of β-adrenoceptor agonists on membrane currents smooth muscle cells from human urinary bladder using a whole-cell patch clamp to investigate involvement Ca<sup>2+</sup>-activated K<sup>+</sup> (K<sub>Ca</sub>) channels in relaxation by β-adrenergic agonists. With 0.05 mmol/l EGTA pipette, depolarizing pulses evoked outward rectifying currents. Isoproterenol (1 µmol/l) significantly increased 75% at +80 mV with pipette solution. BRL...
The primary cilium is a hair-like immotile organelle with specific membrane receptors, including the receptor of Hedgehog signaling, smoothened. organized in preosteoblasts promotes differentiation cells into osteoblasts (osteoblast differentiation) by mediating signaling to achieve bone formation. Notably, 4.1G plasma membrane-associated cytoskeletal protein that plays essential roles various tissues, peripheral nervous system, testis, and retina. However, its function remains unexplored....
Myocardial infarction (MI) and subsequent adverse remodeling cause heart failure. Previously we demonstrated a role for Kit ligand (KL) in improving cardiac function post-MI. KL has two major isoforms; KL-1 is secreted whereas KL-2 predominantly membrane bound. We demonstrate here first that KL-2-deficient mice have worse survival an increased heart/bodyweight ratio post-MI compared to with reduced c-Kit receptor expression. Next synthesized recombinant lentiviral vectors (LVs) engineered...
The primary cilium undergoes cell cycle–dependent assembly and disassembly. Dysregulated ciliary dynamics are associated with several pathological conditions called ciliopathies. Previous studies showed that the localization of phosphorylated Tctex-1 at Thr94 (T94) base critically regulates resorption by accelerating actin remodeling pocket membrane endocytosis. Here, we show microtubule-associated serine/threonine kinase family member 4 (MAST4) is localized cilium. Suppressing MAST4 blocks...