- Muscle Physiology and Disorders
- Influenza Virus Research Studies
- interferon and immune responses
- Protease and Inhibitor Mechanisms
- Virus-based gene therapy research
- Infectious Encephalopathies and Encephalitis
- Respiratory viral infections research
- Muscle metabolism and nutrition
- HIV Research and Treatment
- Exercise and Physiological Responses
- Cell Adhesion Molecules Research
- Heat shock proteins research
- Immune Cell Function and Interaction
- Peptidase Inhibition and Analysis
- Adipose Tissue and Metabolism
- Genetic Neurodegenerative Diseases
- Mast cells and histamine
- RNA modifications and cancer
- RNA Research and Splicing
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- HIV/AIDS drug development and treatment
- RNA Interference and Gene Delivery
- Phytoestrogen effects and research
- Glycosylation and Glycoproteins Research
- Adipokines, Inflammation, and Metabolic Diseases
Sagami Women's University
2015-2021
Tokushima University
2007-2018
Marymount University
2008
Otsuka Pharmaceutical (Spain)
2008
Nagoya University
2004
National Institute for Basic Biology
2004
Hokkaido University
2004
Scripps Research Institute
2002
Autophagy is mostly a nonselective bulk degradation system within cells. Recent reports indicate that autophagy can act both as protector and killer of the cell depending on stage disease or surrounding cellular environment (for review see Cuervo, A.M. 2004. Trends Cell Biol. 14:70–77). We found cytoplasmic vacuoles induced in pancreatic acinar cells by experimental pancreatitis were autophagic origin, demonstrated microtubule-associated protein 1 light chain 3 expression electron microscopy...
Entry of enveloped viruses into host cells requires the activation viral envelope glycoproteins through cleavage by either intracellular or extracellular proteases. In order to gain insight molecular basis protease and its impact on efficiency entry, we investigated susceptibility a recombinant native full-length S-protein trimer (triSpike) severe acute respiratory syndrome coronavirus (SARS-CoV) various airway proteases.PURIFIED TRISPIKE PROTEINS WERE READILY CLEAVED IN VITRO BY THREE...
Skeletal muscle atrophy caused by unloading is characterized both decreased responsiveness to myogenic growth factors (e.g., insulin-like factor 1 [IGF-1] and insulin) increased proteolysis.Here, we show that stress resulted in skeletal through the induction activation of ubiquitin ligase Cbl-b.Upon induction, Cbl-b interacted with degraded IGF-1 signaling intermediate IRS-1.In turn, loss IRS-1 activated FOXO3-dependent atrogin-1/MAFbx, a dominant mediator proteolysis atrophic...
Background It appears to have been well established that after surgery, protein catabolism is accelerated and glucose infusion suppresses the catabolic reactions. However, in early postoperative period, effects of surgical stress on muscle related mechanisms remain unclear. Methods Rats undergoing laparotomy were infused with acetated Ringer's solution (10 ml x kg(-1) h(-1)) without (control) or containing 1% 5% glucose. The was continued for a further 4 h treatment. index, excretion urinary...
Membrane type 1 matrix metalloproteinase (MT1-MMP) was suggested to play a critical role in the regulation of tissue invasion by normal and neoplastic cells directly mediating activation pro-gelatinase A. Recently, proteolytic pro-MT1-MMP an intracellular proprotein convertase, furin, reported. In this study, we found that plasmin efficiently activates cleaving immediately downstream Arg108 Arg111 multi-basic motif between its pro- catalytic domains participates Our present data suggest...
Host cellular proteases induce influenza virus entry into cells by cleaving the viral surface envelope glycoprotein hemagglutinin (HA). However, details on involved in this event are not fully available. We report here that ubiquitous type II transmembrane serine proteases, MSPL and its splice variant TMPRSS13, novel candidates for processing HA proteins of highly pathogenic avian (HPAI) viruses, apart from previously identified furin proprotein convertases 5 6. HAs all HPAI H5 H7 strains...
Hsp70 is often overexpressed in cancer cells, and the selective cellular survival advantage that it confers may contribute to process of tumour formation. Thus, pharmacological manipulation levels cells be an effective means preventing progression tumours. We found downregulation by ibuprofen vitro enhances antitumoural activity cisplatin lung cancer. Ibuprofen prominently suppressed expression A549 derived from adenocarcinoma sensitized them association with increase mitochondrial apoptotic...
Extracellular cleavage of virus envelope fusion glycoproteins by host cellular proteases is a prerequisite for the infectivity mammalian and nonpathogenic avian influenza viruses, Sendai virus. Here we report protease present in airway that, like tryptase Clara, can process A haemagglutinin glycoprotein. This was extracted from membrane fraction rat lungs, purified then identified as mini‐plasmin. Mini‐plasmin distributed predominantly epithelial cells upward divisions bronchioles...
Unloading-mediated muscle atrophy is associated with increased reactive oxygen species (ROS) production. We previously demonstrated that elevated ubiquitin ligase casitas B-lineage lymphoma-b (Cbl-b) resulted in the loss of volume (Nakao R, Hirasaka K, Goto J, Ishidoh Yamada C, Ohno A, Okumura Y, Nonaka I, Yasutomo Baldwin KM, Kominami E, Higashibata Nagano Tanaka Yasui N, Mills EM, Takeda S, Nikawa T. Mol Cell Biol 29: 4798-4811, 2009). However, pathological role ROS production...
Venomous mammals are rare, and their venoms have not been characterized. We purified characterized the blarina toxin (BLTX), a lethal mammalian venom with tissue kallikrein-like activity from submaxillary sublingual glands of short-tailed shrew Blarina brevicauda . Mice administered BLTX i.p. developed irregular respiration, paralysis, convulsions before dying. Based on amino acid sequence protein, we cloned cDNA. It consists prosequence an active form 253 aa typical catalytic triad serine...
The protective effect of ambroxol, a mucolytic agent which has antioxidant properties and stimulates the release pulmonary surfactant, against influenza-virus proliferation in airway was investigated mice. Ambroxol or vehicle administered intraperitoneally twice day for 5-7 days to mice shortly after intranasal infection with lethal dose influenza A/Aichi/68 (H3N2) virus, survival rate, virus titre levels factors regulating fluid were analysed. significantly suppressed multiplication...
The 14-3-3 proteins are highly conserved molecules that function as intracellular adaptors in a variety of biological processes, such signal transduction, cell cycle control, and apoptosis. Here, we show protein is heat-shock (Hsp) protects cells against physiological stress its new cellular function. We have observed that, Drosophila cells, the 14-3-3zeta up-regulated under heat conditions, process mediated by shock transcription factor. As action linked to stress, interacted with...
Intact osteoactivin, a novel type I membrane glycoprotein, were shed at dibasic motif in the juxtamembrane region C2C12 myoblasts. Extracellular fragments secreted into culture media by putative metalloprotease. of but not control protein, induced matrix metalloprotease‐3 (MMP‐3) expression NIH‐3T3 fibroblasts. Epidermal growth factor (ERK) kinase inhibitors inhibited osteoactivin‐mediated MMP‐3 expression, whereas extracellular fragment osteoactivin activated ERK1/2 and p38...
Proinflammatory cytokines are factors that induce ubiquitin-proteasome-dependent proteolysis in skeletal muscle, causing muscle atrophy. Although isoflavones, as potent antioxidative nutrients, have been known to reduce damage during the catabolic state, non-antioxidant effects of isoflavones against atrophy not well known. Here we report on inhibitory such genistein and daidzein caused by tumor necrosis factor (TNF)-α treatment. In C2C12 myotubes, TNF-α treatment markedly elevated...
Although the urokinase receptor (uPAR) binds to vitronectin (VN) and promotes adhesion of cells this matrix protein, biochemical details interaction remain unclear. VN variants were employed in BIAcore experiments examine uPAR-VN detail compare it with other ligands. Heparin plasminogen bound fragments containing heparin-binding domain, indicating that domain was functionally active recombinant peptides. However, no significant binding detected when uPAR incubated neither heparin nor...
Oxidative stress is a key factor in stimulating the expression of atrogenes, which are muscle atrophy-related ubiquitin ligases, skeletal muscle, and it induces atrophy during unloading. However, effects antioxidative nutrients on atrogene have not been demonstrated. We report inhibitory polyphenols, such as epicatechin (EC), gallate (ECg) epigallocatechin (EGCg) quercetin, up-regulated by three dimensional (3D)-clinorotation or glucocorticoid. These treatments markedly elevated including...
Skeletal muscle is one of the most sensitive tissues to mechanical loading, and unloading inhibits regeneration potential skeletal after injury. This study was designed elucidate specific effects stress on function immunocytes during We examined immunocyte infiltration in cardiotoxin (CTX)-injected soleus muscles tail-suspended (TS) mice. In CTX-injected TS mice, cross-sectional area regenerating myofibers smaller than that weight-bearing (WB) indicating delays following CTX-induced damage....
We previously reported the potential involvement of casitas B-cell lymphoma-b (Cbl-b) in aging-related murine insulin resistance. Because obesity also induces macrophage recruitment into adipose tissue, we elucidated here role Cbl-b obesity-related Cbl-b(+/+) and Cbl-b(-/-) mice were fed a high-fat diet (HFD) then examined for changes signaling. The HFD caused macrophages tissue increased inflammatory reaction compared with mice. Peritoneal from Cbl-b-overexpressing RAW264.7 used to examine...
Background. Unloading stress induces skeletal muscle atrophy. We have reported that Cbl-b ubiquitin ligase is a master regulator of unloading-associated The present study was designed to elucidate whether dietary soy glycinin protein prevents denervation-mediated atrophy, based on the presence inhibitory peptides against in protein. Methods. Mice were fed either 20% casein diet, isolate 10% diet containing casein, or diet. One week later, right sciatic nerve cut. wet weight, cross sectional...
Influenza A virus (IAV) is one of the most common infectious pathogens in humans and causes considerable morbidity mortality.The recent spread highly-pathogenic avian IAV H5N1 viruses has reinforced importance pandemic preparedness.In pathogenesis infection, cellular proteases play critical roles process viral entry into cells that subsequently leads to tissue damage infected organs.Since there are no processing protease for membrane fusion glycoprotein hemagglutinin precursor (HA 0 ) IAV,...
Abstract Deficiency of the Cbl‐b ubiquitin ligase gene activates macrophages in mice. This study aimed to elucidate pathophysiological roles muscle degeneration/regeneration ‐deficient We examined immune cell infiltration and cytokine expression cardiotoxin‐injected tibialis anterior Ablation delayed regeneration cardiotoxin‐induced skeletal damage compared with wild‐type CD8‐positive T cells were still present damaged on day 14 after cardiotoxin injection mice, but there was dispersal same...
Endothelin (ET)-1(1-31) is a novel 31-amino acid-length peptide derived from big ET-1 by chymase or other chymotrypsin-type proteases and major ET derivative in human neutrophils. In this study, we revealed that ET-1(1-31), but not ET, exhibited chemotactic activities toward neutrophils monocytes as an inflammatory mediator, although the effects were less potent than those of formyl-methionyl-leucyl-phenylalanine interleukin-8. However, ET-1(1-31) much greater 21-amino acid ET-1, ET-1(1-21)....