A5016838749- Sphingolipid Metabolism and Signaling
- Protein Kinase Regulation and GTPase Signaling
- Cancer, Hypoxia, and Metabolism
- Fibroblast Growth Factor Research
- Cellular transport and secretion
- Nitric Oxide and Endothelin Effects
- Ion channel regulation and function
- Lipid Membrane Structure and Behavior
- Cancer-related Molecular Pathways
- PI3K/AKT/mTOR signaling in cancer
- Receptor Mechanisms and Signaling
- Endoplasmic Reticulum Stress and Disease
- Cell Adhesion Molecules Research
- Retinal Development and Disorders
- Microtubule and mitosis dynamics
- Lipid metabolism and biosynthesis
- Angiogenesis and VEGF in Cancer
- Erythrocyte Function and Pathophysiology
- ATP Synthase and ATPases Research
- Phagocytosis and Immune Regulation
- Protein Tyrosine Phosphatases
- Ion Transport and Channel Regulation
- Metabolism, Diabetes, and Cancer
- Immune cells in cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Kanazawa University
2009-2023
Ishikawa Prefectural Nursing University
2008-2023
Ishikawa Prefectural University
2018-2020
Japanese Society of Physiological Anthropology
2013
The University of Tokyo
1992-2010
Advanced Science Research Center
2010
University of Tsukuba
1989-2010
Kanazawa Medical University
2006
Asahi Chemical & Industry (Japan)
2003
Kitasato University
2003
Abstract Endothelin, a novel vasoactive peptide derived from endothelial cells (Yanagisawa, M., Kurihara, H., Kimura, S., Tomobe, Y., Kobayashi, Mitsui, Yazaki, Goto, K., and Masaki, T. (1988) Nature 332, 411-415), acts as potent mitogen in Swiss 3T3 fibroblasts. The effect is dose-dependent with half-maximal obtained at approximately 3 x 10(-11) M synergistically enhanced by low concentration of insulin-like growth factor-I. Endothelin specifically binds to single class high affinity...
Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid that induces variety of biological responses in diverse cell types. Many, if not all, these are mediated by members the EDG (endothelial differentiation gene) family G protein-coupled receptors EDG1, EDG3, and EDG5 (AGR16). Among prominent activities S1P regulation motility; stimulates or inhibits motility depending on In present study, we provide evidence for subtype-specific, contrasting cellular Rac activity. CHO cells...
Ca2+ sensitization of vascular smooth muscle (VSM) contraction involves Rho-dependent and Rho-kinase-dependent suppression myosin phosphatase activity. We previously demonstrated that excitatory agonists in fact induce activation RhoA VSM. In this study, we demonstrate a novel Ca2+-dependent mechanism for activating rabbit aortic High KCl-induced membrane depolarization as well noradrenalin stimulation induced similar extents sustained Both stimuli also time-dependent, increases the amount...
In Chinese hamster ovary (CHO) cells transiently transfected with an expression vector for EDG1, but not empty vector, sphingosine-1-phosphate (SP) at a concentration as low 10<sup>−10</sup>m caused increase in the intracellular free Ca<sup>2+</sup> ([Ca<sup>2+</sup>]<sub>i</sub>) result of mobilization from both and extracellular pools. CHO clone stably expressing EDG1 receptor (CHO-EDG1 cells), SP induced increases production inositol phosphates [Ca<sup>2+</sup>]<sub>i</sub> inhibited...
The G protein-coupled receptors S1P2/Edg5 and S1P3/Edg3 both mediate sphingosine-1-phosphate (S1P) stimulation of Rho, yet S1P2 but not S1P3 mediates downregulation Rac activation, membrane ruffling, cell migration in response to chemoattractants. Specific inhibition endogenous Gα12 Gα13, Gαq, by expression respective C-terminal peptides abolished S1P2-mediated Rac, migration, as well Rho stress fiber formation. Fusion comprising either or mediated S1P also migration. Overexpression Gαi,...
Previous studies demonstrated that sphingosine-1-phosphate (S1P) induced migration of human umbilical vein endothelial cells (HUVECs) whereas it inhibited vascular smooth muscle (SMCs). This study explored the molecular mechanisms underlying contrasting S1P actions on cell motility. In rat and aortic SMCs, chemoattractant platelet-derived growth factor B-chain (PDGF) rapid 5- to 6-fold increases in cellular amount GTP-bound, active form Rac. did not affect PDGF-stimulated tyrosine...
In the present study, we determined agonist specificity and signalling mechanisms of a putative sphingosine 1-phosphate (S1P) receptor, AGR16. CHO cells transiently transfected with an AGR16 expression vector, but not in empty addition low concentration S1P (1 nM) caused increase intracellular free Ca2+ ([Ca2+]i) by mobilization from both intra- extra-cellular pools. To determine spectrum agonists for AGR16, employed K562 cells, which naive state do respond at all to either or structurally...
The mechanisms of endothelin-1 (ET) actions were investigated in cultured rat aortic vascular smooth muscle A-10 cells. cells have a single class high affinity binding sites for ET with an apparent Mr 65,000-75,000 on SDS-PAGE. Stimulation induces mobilization Ca2+ from both intra- and extracellular pools to produce biphasic increase cytoplasmic free concentration. increases cellular levels inositol trisphosphate 1,2-diacylglycerol, indicating activation phospholipase C by ET. stimulates...
~ ~Bombesin, a peptide mitogen for variety of cell types, acts as typical Ca2+-mobilizing hormone in Swiss 3T3 fibroblasts.At its mitogenic concentrations (1-25 nM), bombesin stimulates polyphosphoinositide turnover, i.e. breakdown phosphatidylinositol 4,5bisphosphate and concomitant increase inositol phosphates time-and dose-dependent manner.In particular, induces an initial transient 1,4,5-trisphosphate concentration, followed by the concentration 1,3,4-trisphosphate.Also, within 30 s...
Sphingosine kinase 1 (SPHK1), its product sphingosine-1-phosphate (S1P), and S1P receptor subtypes have been suggested to play protective roles for cardiomyocytes in animal models of ischaemic preconditioning cardiac ischaemia/reperfusion injury. To get more insight into SPHK1 vivo, we generated SPHK1-transgenic (TG) mice analysed the phenotype.SPHK1-TG overexpressed diverse tissues, with a nearly 20-fold increase enzymatic activity. The TG grew normally normal blood chemistry, cell counts,...
Phosphatidylinositol (PI) 3-kinase is required for G1 to S phase cell cycle progression stimulated by a variety of growth factors and implicated in the activation several downstream effectors, including p70(S6K). However, molecular mechanisms which PI engaged machinery are not well understood. Here we report that expression dominant negative (DN) form either p110alpha catalytic or p85 regulatory subunit heterodimeric strongly inhibited epidermal factor (EGF)-induced upregulation cyclin D1...
AbstractIt is well documented that Ras functions as a molecular switch for reentry into the cell cycle at border between G0 and G1 by transducing extracellular growth stimuli early mitogenic signals. In present study, we investigated role of during late stage phase using NIH 3T3 (M17) fibroblasts in which expression dominant negative mutant, p21Ha-Ras(Asn17), induced response to dexamethasone treatment. We found delaying Ras(Asn17) until introducing 3 h after addition epidermal factor (EGF)...
We investigated mechanisms for inhibition of B16 melanoma cell migration and invasion by sphingosine-1-phosphate (S1P), which is the ligand Edg family G protein-coupled receptors also implicated as an intracellular second messenger. S1P, dihydro-S1P, sphingosylphosphorylcholine inhibited with relative potencies expected S1P2 receptor agonists. The S1P2-selective antagonist JTE013 completely abolished responses to these In addition, abrogated sphingosine, S1P precursor but not agonist...
Small GTPase Rho and its downstream effector, kinase, have been implicated in agonist-stimulated Ca(2+) sensitization of 20-kDa myosin light chain (MLC(20)) phosphorylation contraction smooth muscle. In the present study we demonstrated for first time that excitatory receptor agonists induce increases amounts an active GTP-bound form RhoA, GTP-RhoA, rabbit aortic Using a pull-down assay with recombinant RhoA-binding protein, Rhotekin, found thromboxane A(2) mimetic, U-46619, which induced...
The effects of carbachol on polyphosphoinositides and 1,2-diacylglycerol metabolism were investigated in bovine tracheal smooth muscle by measuring both lipid mass the turnover [3H]inositol-labeled phosphoinositides. Carbachol induces a rapid reduction phosphatidylinositol 4,5-bisphosphate 4-monophosphate increase phosphatidic acid. These changes are sustained for at least 60 min. level shows delayed progressive decrease during 60-min period stimulation. addition atropine reverses these...
Abstract Sphingosine-1-phosphate (S1P) has been implicated in tumor angiogenesis by acting through the Gi-coupled chemotactic receptor S1P1. Here, we report that distinct S1P2 is responsible for mediating G12/13/Rho-dependent inhibitory effects of S1P on Akt, Rac, and cell migration, thereby negatively regulating growth. By using S1P2LacZ/+ mice, found was expressed both normal blood vessels many organs, endothelial cells (EC) vascular smooth muscle cells, as well tumor-associated,...
Mechanical strain has been implicated in phenotypic changes, including alteration of gene expression vascular smooth muscle cells; however, the molecular basis for mechanotransduction leading to nuclear is largely unknown. We demonstrate present study that cyclic stretching cells dramatically activates Jun N-terminal kinase (JNK)/stress-activated protein (SAPK) through an autocrine mechanism. Stretch causes time- and strength-dependent rise ATP concentration media. The stretch-induced...