A5089905179- Cancer, Hypoxia, and Metabolism
- Angiogenesis and VEGF in Cancer
- Receptor Mechanisms and Signaling
- Mesenchymal stem cell research
- Eicosanoids and Hypertension Pharmacology
- Cardiac electrophysiology and arrhythmias
- Inflammatory mediators and NSAID effects
- Nitric Oxide and Endothelin Effects
- Cellular transport and secretion
- RNA and protein synthesis mechanisms
- Ion channel regulation and function
- Protein Kinase Regulation and GTPase Signaling
- Caveolin-1 and cellular processes
- Metabolism, Diabetes, and Cancer
- Muscle Physiology and Disorders
- Autophagy in Disease and Therapy
- Heart Failure Treatment and Management
- Glycosylation and Glycoproteins Research
- Atherosclerosis and Cardiovascular Diseases
- Tissue Engineering and Regenerative Medicine
- Cardiomyopathy and Myosin Studies
- Adipokines, Inflammation, and Metabolic Diseases
- Extracellular vesicles in disease
- Neurobiology and Insect Physiology Research
- Renin-Angiotensin System Studies
Asahikawa Medical University
2015-2025
Asahikawa Medical College Hospital
2000-2023
Asahikawa University
2014-2019
Kanagawa Cardiovascular and Respiratory Center
2018
Osaka Medical and Pharmaceutical University
2010
Toshiba (Japan)
2010
Massachusetts General Hospital
2010
Harvard University
1996-2010
Yokohama City University
2004-2007
New Jersey Institute of Technology
2007
A novel adenylylcyclase cDNA (type V) was isolated from a canine heart library. Northern blotting indicates that the expression of this message is most abundant in with lesser amount brain but absent variety other tissues including lung, kidney, skeletal muscle, lymphocyte, and testis. The putative protein product predicted sequence has motif tandem six-transmembrane spans separated by large hydrophilic cytoplasmic loop as seen members family. When expressed using CMT cell transient system,...
Caveolar localization of protein kinase C and the regulation caveolar function by are well known. This study was undertaken to examine whether caveolin subtypes interact with various isoenzymes using scaffolding domain peptide. When C-alpha, -epsilon, -zeta were overexpressed in COS cells followed subcellular fractionation sucrose gradient method, all (alpha, epsilon, zeta) detected same fraction as caveolin. The peptide caveolin-1 -3, but not -2, inhibited activity autophosphorylation...
Cyclic AMP production within cells is altered upon protein kinase C (PKC) activation; however, whether PKC directly modulates adenylyl cyclase (AC) catalytic activity has been controversial. Molecular studies have elucidated the existence of multiple isoenzymes although functional role this diversity not clear. Using purified and AC isoenzymes, we demonstrate that zeta phosphorylates type VAC, leading to an approximate 20-fold increase in its activity, a significantly larger enhancement than...
The changing relationship between stimuli and responses after prolonged receptor stimulation is a general feature of hormonal signaling systems, termed desensitization. This phenomenon has been best exemplified in the covalent modification G protein-linked catecholamine receptors. However, other components within this pathway can be involved Here we present evidence that desensitization occurs at level effector enzyme itself through phosphorylation. Type V adenylyl cyclase (AC) major isoform...
A sixth member of the mammalian adenylyl cyclase family has been isolated from a canine cardiac cDNA library. This isoform is more highly homologous to type V than other types; sequence similarity apparent even in transmembrane regions where greatest divergence among types exists. Type VI mRNA expression most abundant heart and brain; however, unlike V, low level also observed variety tissues examined. can be stimulated by NaF, guanosine 5'-[gamma-thio]triphosphate, forskolin but not...
The sympathetic nervous system is designed to respond stress. Adenylyl cyclase (AC) the keystone of transmission, yet its role in response acute overload heart or pathogenesis failure controversial. We examined effects pressure overload, induced by thoracic aortic banding, mice which type 5 AC, a major cardiac AC isoform, was disrupted ( AC5 – / ). Left ventricular weight/tibial length ratio (LVW/TL) not different between WT and at baseline increased progressively similarly both groups 1 3...
Desensitization of the cyclic adenosine monophosphate signal protects cardiac myocytes against catecholamine stress, thus preventing development apoptosis. Molecular mechanisms desensitization have been well studied at level adrenergic receptors but less so effector enzyme, adenylyl cyclase (AC).When effects long-term (1 to 2 weeks) isoproterenol infusion were compared between type 5 AC-null mice (AC5KO) and wild-type controls, we found that subsequent responses left ventricular ejection...
In a genetically engineered mouse line with disruption of type 5 adenylyl cyclase (AC5-/-), major cardiac isoform, there was no compensatory increase in other isoforms AC the heart. Both basal and isoproterenol (ISO)-stimulated activities were decreased by 30% to 40% membranes. The reduced activity did not affect function (left ventricular ejection fraction [LVEF]) at baseline. However, increases LVEF after ISO significantly attenuated AC5-/- (P<0.05, n=11). Paradoxically, conscious mice had...
Various neurotransmitters, such as dopamine, stimulate adenylyl cyclase to produce cAMP, which regulates neuronal functions. Genetic disruption of the type 5 isoform led a major loss activity in striatum-specific manner with small increase expression few other isoforms. D1 dopaminergic agonist-stimulated was attenuated, and this accompanied by decrease receptor Gsα. D2 agonist-mediated inhibition also blunted. Type cyclase-null mice exhibited Parkinsonian-like motor dysfunction, i.e....
Type 2 diabetes is preceded by the development of insulin resistance, in which action impaired, largely skeletal muscles. Caveolin-3 (Cav3) a muscle-specific subtype caveolin, an example scaffolding protein found within membranes. Cav also known as growth signal inhibitor, although it was recently demonstrated that genetic disruption Cav3 did not augment mice. We found, however, lack led to exemplified decreased glucose uptake muscles, impaired tolerance test performance, and increases serum...
The hedgehog (Hh) pathway has been implicated in the pathogenesis of cancer including pancreatic ductal adenocarcinoma (PDAC). Recent studies have suggested that oncogenic function Hh PDAC involves signaling stromal cells rather than cell autonomous effects on tumor cells. However, origin and nature type(s) are responsive to remained unknown. Since plays a crucial role during embryonic postnatal vasculogenesis, we speculated ligand may act vasculature specifically focusing bone marrow...
Abstract The recent emergence of in vitro microvessel models has boosted research on angiogenesis and vascularization tissue engineering, due to their superior control over controlling culture conditions enabling real-time observation compared vivo models. However, conventional two-dimensional (2D) analysis fail capture the heterogeneity three-dimensional (3D) morphological dynamics. To overcome this issue, here, a novel registration method for spatiotemporal quantification angiogenic...
Mutations in the cardiac Na+ channel gene SCN5A are responsible for multiple lethal ventricular arrhythmias including Brugada syndrome and congenital long QT syndrome. Here we report a case of with ST elevation right precordial inferior leads accompanied by atrial standstill spontaneous fibrillation. Atrial J wave were provoked procainamide. Genetic analysis revealed missense mutation (R367H) SCN5A. The resultant mutant was nonfunctional when expressed heterologously Xenopus oocytes. Our...
Background Cytokines induce apoptosis in vascular disease lesions through enhancement of inducible nitric oxide (NO) synthase (iNOS) activation. The thiazolidinediones, novel insulin-sensitizing agents, have been demonstrated to modulate cytokine-induced NO production. We investigated the role pioglitazone smooth muscle cells (VSMCs) vitro and developed intimal hyperplasia vivo. Methods Results Pioglitazone (0.1 10 μmol/L) significantly enhanced expression iNOS production a dose-dependent...
Neuronal nicotinic acetylcholine receptors (nAChRs) are made of multiple subunits with diversified functions. The nAChR alpha 7-subunit has a property high Ca2+ permeability and may have specific functions localization within the plasma membrane as signal transduction molecule. In PC-12 cells, fractionation by sucrose gradient centrifugation revealed that 7 existed in low-density, cholesterol-enriched microdomains known lipid rafts where flotillin also exists. contrast, 5- beta2-subunits...
Mechanical stress contributes to vascular disease related hypertension. Activation of ERK is key mediating cellular proliferation and remodeling in response stretch stress. However, the mechanism by which mediates activation tissue still unclear. Caveolin, a major component flasklike invaginated caveolae, acts as an adaptor protein for integrin-mediated signaling pathway. We found that cyclic transiently induced translocation caveolin from caveolae noncaveolar membrane sites smooth muscle...
Type V adenylyl cyclase (AC) was stably over‐expressed in HEK293 cells (293AC‐V). Forskolin‐stimulated cAMP accumulation 293AC‐V 5 times as great that control cells. PMA, a protein kinase C (PKC) activator, enhanced dose‐and time‐dependently and this enhancement abolished by staurosporine. Insulin also Co‐transfection of PKC‐ζ, but not PKC‐α, potentiated the effects insulin. These data suggest type AC activity is regulated PKC isoenzymes through different extracellular stimuli.
Prostacyclin (PGI2) enhances angiogenesis, especially in cooperation with bone marrow (BM)-derived endothelial progenitor cells (EPCs). However, the mechanisms of PGI2 EPC-mediated angiogenesis vivo remain unclear. The purpose this study was to clarify role using BM-specific IP deletion mice.Hind limb ischemia (HLI) induced wild-type (WT) mice transplanted IP-deleted BM (WT/BM(IP(-/-)). Recovery blood flow (RBF) WT/BM(IP(-/-)) impaired for 28 days after HLI, whereas RBF IP(-/-)/BM(WT)...
Angiogenesis, which refers to the formation of new blood vessels from already existing vessels, is a promising therapeutic target and complex multistep process involving many different factors. Pericytes (PCs) are attracting attention as they considered make significant contributions maturation stabilisation newly formed although not much known about precise mechanisms involved. Since there no single specific marker for pericytes, in vivo models may complicate PC identification study PCs...