A5009001273- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Nitric Oxide and Endothelin Effects
- Immune Response and Inflammation
- Immune cells in cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Phagocytosis and Immune Regulation
- Adenosine and Purinergic Signaling
- Blood disorders and treatments
- Advanced Glycation End Products research
- Cell Adhesion Molecules Research
- Viral-associated cancers and disorders
- Advanced Nanomaterials in Catalysis
- Autophagy in Disease and Therapy
- Receptor Mechanisms and Signaling
- Redox biology and oxidative stress
- Ion Channels and Receptors
- S100 Proteins and Annexins
- Angiogenesis and VEGF in Cancer
- Cytomegalovirus and herpesvirus research
- Complement system in diseases
- HIV Research and Treatment
- Biochemical Acid Research Studies
- Sphingolipid Metabolism and Signaling
- Phenothiazines and Benzothiazines Synthesis and Activities
- Legionella and Acanthamoeba research
Kawasaki Medical School
2020-2025
Kyushu University
2009-2023
The University of Tokyo
2014
Cohort (United Kingdom)
2010
Japan Science and Technology Agency
2005-2007
Ehime University
2001-2007
Aichi Medical University
2004
Fujita Health University
2004
Emory University
2001
Nox3, a member of the superoxide-producing NADPH oxidase (Nox) family, participates in otoconia formation mouse inner ears, which is required for perception balance and gravity. The activity other Nox enzymes such as gp91(phox)/Nox2 Nox1 known to absolutely require both an organizer protein (p47(phox) or Noxo1) andanactivatorprotein (p67(phox) Noxa1); p47(phox)-dependent activation these oxidases, treatment cells with stimulants phorbol 12-myristate 13-acetate also indispensable. Here we...
Abstract Reactive oxygen species (ROS) produced by NADPH oxidase 2 (Nox2) function as key mediators of mechanotransduction during both physiological adaptation to mechanical load and maladaptive remodeling the heart. This is despite low levels cardiac Nox2 expression. The mechanism underlying transition from maladaptation remains obscure, however. We demonstrate that transient receptor potential canonical 3 (TRPC3), a Ca 2+ -permeable channel, acts positive regulator ROS (PRROS) in...
Activation of the non-phagocytic superoxide-producing NADPH oxidase Nox1, complexed with p22phox at membrane, requires its regulatory soluble proteins Noxo1 and Noxa1. However, role small GTPase Rac remained to be clarified. Here we show that directly participates in Nox1 activation via interacting Electropermeabilized HeLa cells, ectopically expressing Noxo1, Noxa1, produce superoxide a GTP-dependent manner, which is abrogated by expression mutant Noxa1(R103E), defective binding. Superoxide...
Abstract Structural cardiac remodeling, accompanying cytoskeletal reorganization of cells, is a major clinical outcome diastolic heart failure. A highly local Ca 2+ influx across the plasma membrane has been suggested to code signals induce Rho GTPase-mediated fibrosis, but it obscure how specifically decodes as reorganizing signal under conditions rhythmic handling required for pump function. We found that an inhibition transient receptor potential canonical 3 (TRPC3) channel activity...
Hydrogen peroxide (H2O2), a member of reactive oxygen species (ROS), plays diverse physiological roles including host defense and cellular signal transduction. During ingestion invading microorganisms, professional phagocytes such as macrophages release H2O2 specifically into the phagosome to direct toxic ROS toward engulfed microbes. Although is considered exert discrete effects in living systems depending on location its production, accumulation, consumption, there have been limitations...
Neutrophils are highly motile leukocytes that play important roles in the innate immune response to invading pathogens. rapidly migrate site of infections and kill pathogens by producing reactive oxygen species (ROS). Neutrophil chemotaxis ROS production require activation Rac small GTPase. DOCK2, an atypical guanine nucleotide exchange factor (GEF), is one major regulators neutrophils. However, because DOCK2 deficiency does not completely abolish fMLF-induced activation, other GEFs may also...
Rac1 and Rac2, which belong to the Rho subfamily of Ras-related GTPases, play an essential role in activation gp91phox/Nox2 (cytochrome b-245, β polypeptide; also known as Cybb), catalytic core superoxide-producing NADPH oxidase phagocytes. contributes non-phagocytic oxidases Nox1 (NADPH 1) Nox3 3), each related closely gp91phox/Nox2. It has remained controversial whether insert region Rac (amino acids 123–135), unique proteins, is involved activation. In present study we show that removal...
Activation of the neutrophil NADPH oxidase occurs via assembly cytosolic regulatory proteins p47phox, p67phox, and Rac with membrane-associated flavocytochrome b 558. Following cell-free activation, enzymatic activity is highly labile (Tamura, M., Takeshita, Curnutte, J. T., Uhlinger, D. J., Lambeth, (1992) Biol. Chem. 267, 7529–7538). To try to stabilize investigate nature complex, fusion between p47N-(1–286) p67N-(1–210) were constructed. In a system, protein, p67N-p47N, had an 8-fold...
The superoxide-producing NADPH oxidase in phagocytes is crucial for host defence; its catalytic core the membrane-integrated protein gp91phox [also known as Nox2 (NADPH 2)], which forms a stable heterodimer with p22phox. Activation of requires membrane translocation three cytosolic proteins p47phox, p67phox and small GTPase Rac. At membrane, these assemble gp91phox-p22phox induce conformational change gp91phox, leading to superoxide production. p47phox translocates membranes using two...
The phagocyte NADPH oxidase, dormant in resting cells, is activated during phagocytosis to produce superoxide, a precursor of microbicidal oxidants. membrane-integrated protein gp91(phox) serves as the catalytic core, because it contains complete electron-transporting apparatus from molecular oxygen for superoxide production. Activation requires cytosolic proteins p67(phox), p47(phox), and Rac (a small GTPase). comprising 526 amino acids, moves upon cell stimulation membrane together with...
Activation of the phagocyte NADPH oxidase, a superoxide-generating enzyme, involves assembly cytosolic p47phox, p67phox, and rac with membrane-associated cytochrome b558. Following cell-free activation, enzymatic activity is highly labile [Tamura, M., Takeshita, Curnutte, J. T., Uhlinger, D. J., Lambeth, (1992) Biol. Chem. 267, 7529−7538]. In an attempt to stabilize investigate nature complex, we have produced fusion proteins between C-terminal truncated form p67phox (residues 1−210, 67N),...
Neutrophils play an essential role via phagocytosis in host defense against microbial infections. However, little is known about molecular mechanisms underlying neutrophils, because of the difficulty genetically manipulating these cells. Here, we provide first comprehensive description phospholipid metabolism during human which have efficiently transfected with cDNAs encoding lipid-probing protein modules. Phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)), F-actin organizer abundant...
A series of truncated forms His6-tagged gp91phox were expressed, solubilized, and purified in the presence 30 μM FAD. The with longest sequence C-terminal region (221−570) (gp91C) showed highest activity (turnover rate, 0.92) for NADPH diaphorase either 0.3% Triton X-100 or 0.5% Genapol X-80. Activity was not inhibited by superoxide dismutase but blocked an inhibitor respiratory burst oxidase, diphenylene iodonium. flavinated gp91C contained approximately 0.9 mol FAD/mol protein (MW 46 kDa)...
The phagocyte NADPH oxidase, crucial for innate immunity, is dormant in resting cells, but becomes activated during phagocytosis to produce superoxide, a precursor of microbicidal oxidants. In activation the multidomain protein p67<sup>phox</sup>plays central role: it translocates membrane as ternary complex with p47<sup>phox</sup>and p40<sup>phox</sup>, and interacts small GTPase Rac assemble membrane-integrated catalytic gp91<sup>phox</sup>,...
Proper mitotic spindle orientation requires that astral microtubules are connected to the cell cortex by microtubule-binding protein NuMA, which is recruited from cytoplasm. Cortical recruitment of NuMA at least partially mediated via direct binding adaptor LGN. LGN normally adopts a closed conformation an intramolecular interaction between its N-terminal NuMA-binding domain and C-terminal region contains four GoLoco (GL) motifs, each capable membrane-anchored Gαi subunit heterotrimeric G...