A5032978645- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Ion Channels and Receptors
- Pulmonary Hypertension Research and Treatments
- Ion Transport and Channel Regulation
- Neuroscience and Neuropharmacology Research
- Caveolin-1 and cellular processes
- Nitric Oxide and Endothelin Effects
- Neuroscience and Neural Engineering
- Mitochondrial Function and Pathology
- Circadian rhythm and melatonin
- Photoreceptor and optogenetics research
- Neurobiology and Insect Physiology Research
- Protein Kinase Regulation and GTPase Signaling
- Receptor Mechanisms and Signaling
- Nicotinic Acetylcholine Receptors Study
- Biochemical Analysis and Sensing Techniques
- Neuroendocrine regulation and behavior
- ATP Synthase and ATPases Research
- Adipose Tissue and Metabolism
- Magnesium in Health and Disease
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Barrier Structure and Function Studies
- Phytochemicals and Antioxidant Activities
- Connexins and lens biology
Nagoya City University
2016-2025
Pharmac
1999-2023
Kinjo Gakuin University
2012-2016
University of Illinois Chicago
2011-2016
University of Calgary
2015
Osaka City University
2014
Kyoto Pharmaceutical University
2013
Soochow University
2012
University of California, San Diego
2012
First Affiliated Hospital of Soochow University
2012
Reactive oxygen species (ROS) derived from NADPH oxidase (NOX) and mitochondria play a critical role in growth factor-induced switch quiescent to an angiogenic phenotype endothelial cells (ECs). However, how highly diffusible ROS produced different sources can coordinate stimulate VEGF signaling drive the process remains unknown. Using cytosol- mitochondria-targeted redox-sensitive RoGFP biosensors with real-time imaging, here we show that stimulation human ECs rapidly increases cytosolic...
Bitter taste perception is a conserved chemical sense against the ingestion of poisonous substances in mammals. A multigene family G-protein-coupled receptors, T2R (so-called TAS2R or TRB) receptors and G-protein alpha subunit (Galpha), gustducin, are believed to be key molecules for its perception, but little known about molecular basis interaction. Here, we use heterologous expression system determine specific domain gustducin necessary coupling. Two chimeric Galpha16 proteins harboring 37...
The ubiquitin E3 protein ligase Nedd4-2 is a physiological regulator of the epithelial sodium channel ENaC, which essential for transepithelial Na+ transport and linked to Liddle's syndrome, an autosomal dominant disorder human salt-sensitive hypertension. function negatively regulated by phosphorylation via serum- glucocorticoid-inducible kinase (Sgk1), serves as mechanism inhibit ubiquitination-dependent degradation ENaC. We report here that 14-3-3 proteins participate in this regulatory...
Rationale: A rise in cytosolic Ca 2+ concentration ([Ca ] cyt ) pulmonary arterial smooth muscle cells (PASMC) is an important stimulus for vasoconstriction and vascular remodeling. Increased resting [Ca enhanced influx have been implicated PASMC from patients with idiopathic hypertension (IPAH). Objective: We examined whether the extracellular -sensing receptor (CaSR) involved proliferation IPAH-PASMC blockade of CaSR inhibits experimental hypertension. Methods Results: In normal superfused...
Hypoxic pulmonary vasoconstriction (HPV) is an important physiological response that optimizes the ventilation/perfusion ratio. Chronic hypoxia causes vascular remodeling, which central to pathogenesis of hypoxia-induced hypertension (HPH). We have previously shown Notch3 up-regulated in HPH and activation Notch signaling enhances store-operated Ca(2+) entry (SOCE), mechanism contributes arterial smooth muscle cell (PASMC) proliferation contraction. Here, we investigate role HPV enhancement...
The transient receptor potential melastatin subfamily (TRPM), which is a mammalian homologue of cell death-regulated genes in Caenorhabditis elegans and Drosophila, has roles the process cycle regulation Ca(2+) signaling. Among this subfamily, TRPM8 (also known as Trp-p8) Ca(2+)-permeable channel that was originally identified prostate-specific gene upregulated tumors. Here we showed expressed human melanoma G-361 cells, activation produced sustainable influx. application menthol, an agonist...
Activation of platelets by thrombin results in a dramatic increase tyrosine phosphorylation on multiple cellular proteins (Ferrell,
We have separated multiple small Mr GTP-binding proteins (G proteins) from bovine brain membranes by several column chromatographies and purified to near homogeneity four of them, including a novel 24,000 G protein (smg p25A), 22,000 p21), the rho (rho p20), c-Ki-ras (c-Ki-ras p21). Among these proteins, only smg p21 is phosphorylated stoichiometrically cAMP-dependent kinase (protein A), extent A in cell-free system. None p25A, p20, other partially A. Neither nor are C. About 1 mol phosphate...
An increase in cytosolic free Ca(2+) concentration ([Ca(2+)]cyt) pulmonary arterial smooth muscle cells (PASMC) is a major trigger for vasoconstriction and critical stimulation PASMC proliferation migration. Previously, we demonstrated that expression function of calcium sensing receptors (CaSR) from patients with idiopathic hypertension (IPAH) animals experimental (PH) were greater than normal subjects control animals. However, the mechanisms by which CaSR triggers influx implication...
K+ is the most abundant metal ion in cells, and changes of [K+] around cell membranes play important roles physiological events. However, there no practical method to selectively visualize at surface cells. To address this issue, we have developed a protein-coupled fluorescent probe for K+, TLSHalo. TLSHalo responsive range, with good selectivity over Na+ retains its K+-sensing properties after covalent conjugation HaloTag protein. By using cells expressing on plasma membrane, successfully...
Electrical events and intracellular calcium concentration ([Ca 2+ ]) imaged using fluo‐3 laser scanning confocal microscopy were simultaneously monitored in single smooth muscle cells freshly isolated from guinea‐pig vas deferens or urinary bladder. Images obtained every 8 ms, during stepping ‐60 to 0 +10 mV for 50 ms under voltage clamp, showed that a rise [Ca ] could be detected within 20 of depolarization five twenty small (< 2 μm diameter) ‘hot spots’, over 95 % which located 1.5 the...
The relationship between Ca 2+ sparks spontaneously occurring at rest and local transients elicited by depolarization was analysed using two‐dimensional confocal images of single smooth muscle cells isolated from guinea‐pig vas deferens urinary bladder. current activation these events also recorded simultaneously under whole‐cell voltage clamp. Spontaneous transient outward currents (STOCs) were detected ‐40 mV in approximately 50 % myocytes either type. corresponding STOCs occurred...
An increase in cytosolic Ca 2+ concentration ([Ca ] cyt ) pulmonary arterial smooth muscle cells (PASMC) is a major trigger for vasoconstriction and an important stimulus medial hypertrophy patients with idiopathic hypertension (IPAH). Vascular (SMC) sense the blood flow shear stress through interstitial fluid driven by pressure or direct exposure to case of endothelial injury. Mechanical can [Ca . Here we report that raised PASMC, while stress-mediated rise protein expression level TRPM7...
L-type voltage-dependent Ca(2+) channels (LVDCC) and large conductance Ca(2+)-activated K(+) (BKCa) are the major factors defining membrane excitability in vascular smooth muscle cells (VSMCs). The release from sarcoplasmic reticulum through ryanodine receptor significantly contributes to BKCa activation VSMCs. In this study direct coupling between LVDCC (Cav1.2) role of caveoline-1 on their interaction mouse mesenteric artery SMCs were examined. by influx was demonstrated patch clamp...
Elevation of intracellular Ca2+ concentration ([Ca2+]i) activates Ca2+/calmodulin-dependent kinases (CaMK) and promotes gene transcription. This signaling pathway is referred to as excitation–transcription (E-T) coupling. Although vascular myocytes can exhibit E-T coupling, the molecular mechanisms physiological/pathological roles are unknown. Multiscale analysis spanning from single molecules whole organisms has revealed essential steps in mouse myocyte Upon a depolarizing stimulus, influx...
Cellular turnover of brain capillary endothelial cells (BCECs) by the balance cell proliferation and death is essential for maintaining homeostasis blood-brain barrier. Stimulation metabotropic ATP receptors (P2Y) transiently increased intracellular Ca²(+) concentration ([Ca²(+)](i)) in t-BBEC 117, a line derived from bovine BCECs. The [Ca²(+)](i) rise induced membrane hyperpolarization via activation apamin-sensitive small-conductance Ca²(+)-activated K(+) channels (SK2) enhanced 117. Here,...
Rationale: An increase in cytosolic free Ca 2+ concentration ([Ca ] cyt ) pulmonary arterial smooth muscle cells (PASMC) is a major trigger for vasoconstriction and an important stimulus PASMC proliferation vascular remodeling. The dihydropyridine channel blockers, such as nifedipine, have been used treatment of idiopathic hypertension (IPAH). Objective: Our previous study demonstrated that the -sensing receptor (CaSR) was upregulated extracellular -induced [Ca enhanced from patients with...
The amiloride-sensitive epithelial Na+ channel (ENaC) controls transport into cells and across epithelia. So far, four homologous subunits of mammalian ENaC have been isolated are denoted as α, β, γ, δ. ENaCδ can associate with β γ generate a constitutive current that is 2 orders magnitude larger than homomeric ENaCδ. However, the distribution pattern not consistent subunits. expressed mainly in brain contrast to subunits, which non-neuronal tissues. To explain this discrepancy, we searched...
Although recent studies show that the 14-3-3 protein is a negative regulator of ubiquitin E3 ligases, molecular mechanism remains largely unknown. We previously demonstrated specifically binds one enzymes, Nedd4-2 (a human gene product KIAA0439, termed hNedd4-2), which can be phosphorylated by serum glucocorticoid-inducible kinase 1 (SGK1); this binding protects phosphorylated/inactive hNedd4-2 from phosphatase-catalyzed dephosphorylation [Ichimura, T., et al. (2005) J. Biol. Chem. 280,...
In articular cartilage inflammation, histamine release from mast cells is a key event. It can enhance cytokine production and matrix synthesis also promote cell proliferation by stimulating chondrocytes. this study, the functional impact of Ca(2+)-activated K(+) (K(Ca)) channels in regulation intracellular Ca(2+) concentration ([Ca(2+)](i)) chondrocytes response to was examined using OUMS-27 cells, as model derived human chondrosarcoma. Application induced significant [Ca(2+)](i) rise...