Toshiro Okazaki

ORCID: 0000-0002-1667-841X
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About
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Research Areas
  • Sphingolipid Metabolism and Signaling
  • Lipid Membrane Structure and Behavior
  • Erythrocyte Function and Pathophysiology
  • Immune Cell Function and Interaction
  • Phagocytosis and Immune Regulation
  • Cell death mechanisms and regulation
  • Autophagy in Disease and Therapy
  • Caveolin-1 and cellular processes
  • Lipid metabolism and biosynthesis
  • T-cell and B-cell Immunology
  • Endoplasmic Reticulum Stress and Disease
  • Retinoids in leukemia and cellular processes
  • Acute Myeloid Leukemia Research
  • Biomedical Research and Pathophysiology
  • Cellular transport and secretion
  • Pancreatic function and diabetes
  • Lysosomal Storage Disorders Research
  • Cell Adhesion Molecules Research
  • Microtubule and mitosis dynamics
  • Platelet Disorders and Treatments
  • Chemokine receptors and signaling
  • RNA Interference and Gene Delivery
  • Immune Response and Inflammation
  • Protein Kinase Regulation and GTPase Signaling
  • Neuroinflammation and Neurodegeneration Mechanisms

Yamaguchi University
2023-2024

Kanazawa Medical University
2013-2022

Ishikawa Prefectural University
2019-2022

Kyoto University
1997-2022

Tottori University
2005-2022

National Institute of Infectious Diseases
2022

Tokyo University of the Arts
2022

The University of Tokyo
2022

Hokkaido University
2005-2021

Kanazawa Medical University Hospital
2020

Sphingolipid metabolism was examined in human promyelocytic leukemia HL-60 cells. Differentiation of cells with 1 alpha, 25-dihydroxyvitamin D3 (vitamin D3; 100 nM) accompanied by sphingomyelin turnover. Maximum turnover [3H]choline-labeled occurred 2 h following vitamin treatment, levels decreasing to 77 +/- 6% control and returning base-line 4 h. Ceramide phosphorylcholine were concomitantly generated. mass increased 55% at treatment returned The amount produced equaled the hydrolyzed,...

10.1016/s0021-9258(19)47268-2 article EN cc-by Journal of Biological Chemistry 1989-11-01

The treatment of HL-60 myelocytic leukemia cells with 1 alpha,25-dihydroxyvitamin D3 (1,25-(OH)2D3) resulted in the activation a neutral sphingomyelinase and sphingomyelin turnover (Okazaki, T., Bell, R., Hannun, Y. (1989) J. Biol. Chem. 264, 19076-19080). In this paper, effects 1,25-(OH)2D3 on product hydrolysis, ceramide, possible function ceramide as lipid mediator cell differentiation were investigated. Treatment time- dose-dependent increase mass levels. Ceramide levels peaked at 2 h...

10.1016/s0021-9258(18)55472-7 article EN cc-by Journal of Biological Chemistry 1990-09-01

Two novel synthetic tetrapeptides, VEID-CHO and DMQD-CHO, could selectively inhibit caspase-6 caspase-3, respectively. We used these inhibitors to dissect the pathway of caspase activation in Fas-stimulated Jurkat cells identify roles each active apoptotic processes. Affinity labeling techniques revealed a branched protease cascade which caspase-8 activates caspase-3 -7, turn, caspase-6. Both -3 have major nuclear apoptosis. Caspase-6 cleaves mitotic apparatus protein (NuMA) mediates...

10.1084/jem.187.4.587 article EN The Journal of Experimental Medicine 1998-02-16

Abstract Leukocyte adhesion and trafficking at the endothelium requires both cellular molecules chemotactic factors. A newly identified CX3C chemokine, fractalkine, expressed on activated endothelial cells, plays an important role in leukocyte migration. We examined functional effects of fractalkine β1 β2 integrin-mediated using a macrophage-like cell line, THP-1 cells. In this study, we report that cells express mRNA encoding receptor for CX3CR1, determined by Northern blotting. Scatchard...

10.4049/jimmunol.164.8.4313 article EN The Journal of Immunology 2000-04-15

Sphingomyelin (SM) synthase has been assumed to be involved in both cell death and survival by regulating pro-apoptotic mediator ceramide pro-survival diacylglycerol. However, its precise functions are ambiguous due the lack of molecular cloning SM gene(s). We isolated WR19L/Fas-SM(-) mouse lymphoid cells, which show a defect at plasma membrane activity resistance induced an SM-directed cytolytic protein lysenin. cells were also highly susceptible methyl-β-cyclodextrin (MβCD) as compared...

10.1074/jbc.m401205200 article EN cc-by Journal of Biological Chemistry 2004-04-01

Treatment of HL-60 cells with a 1 alpha,25-dihydroxyvitamin D3 induces activation neutral sphingomyelinase (SMase), resulting in decrease sphingomyelin (SM) levels and an increase ceramide proposed cycle cell regulation (Okazaki, T., Bell, R., Hannun, Y. (1989) J. Biol. Chem. 264, 19076-19080). Cell-permeable synthetic ceramides induce differentiation toward monocytic lineage without conversion to sphingosine, suggesting that is lipid mediator Bielawska, A., (1990) 265, 15823-15831). In this...

10.1016/s0021-9258(17)41744-3 article EN cc-by Journal of Biological Chemistry 1994-02-01

Ceramide has emerged as a novel lipid mediator in cell proliferation, differentiation, and apoptosis. In this work, we demonstrate that the levels of c-jun mRNA, c-Jun protein, DNA binding activity nuclear transcription factor AP-1 to 12-o-tetradecanoylphorbol 13-acetate responsive elements all increased following treatment with cell-permeable ceramide, N-acetylsphingosine human leukemia HL-60 cells. N-Acetylsphingosine (1-10 μM) mRNA dose-dependent manner, maximal expression was achieved 1...

10.1074/jbc.270.45.27326 article EN cc-by Journal of Biological Chemistry 1995-11-01

Sphingomyelin synthase 1 (SMS1) catalyzes the conversion of ceramide to sphingomyelin. Here, we generated and analyzed SMS1-null mice. mice exhibited moderate neonatal lethality, reduced body weight, loss fat tissues mass, suggesting that they might have metabolic abnormality. Indeed, analysis on glucose metabolism revealed showed severe deficiencies in insulin secretion. Isolated mutant islets severely impaired ability release insulin, dependent stimuli. Further indicated mitochondria islet...

10.1074/jbc.m110.179176 article EN cc-by Journal of Biological Chemistry 2010-11-30

The role of "sphingolipid rheostat" by ceramide and sphingosine 1-phosphate (S1P) in the regulation autophagy remains unclear. In human leukemia HL-60 cells, amino acid deprivation (AA(-)) caused with an increase sphingomyleinase (SMase) activity ceramide, which serves as inducing lipid. Knockdown SMase significantly suppressed induction. S1P treatment counteracted induction AA(-) or C(2)-ceramide. promoted mammalian target rapamycin (mTOR) dephosphorylation/inactivation, autophagy. mTOR...

10.1074/jbc.m112.416552 article EN cc-by Journal of Biological Chemistry 2012-10-04

Ceramide is now recognized as an intracellular lipid signal mediator, which induces various kinds of cell functions including apoptosis. Ceramide-induced apoptosis was reported to be blocked by 12-O-tetradecanoylphorbol 13-acetate, a protein kinase C (PKC) activator, but its mechanism remained unclear. Therefore, we investigated whether ceramide has any effects on PKC in the induction We here report that N-acetylsphingosine (synthetic membrane-permeable ceramide) induced translocation PKC-δ...

10.1074/jbc.272.4.2452 article EN cc-by Journal of Biological Chemistry 1997-01-01

Engagement of the Fas receptor (CD95) initiates multiple signaling pathways that lead to apoptosis, such as formation death-inducing complex (DISC), activation caspase cascades, and generation lipid messenger, ceramide. Sphingomyelin (SM) is a major component rafts, which are specialized structures enhance efficiency membrane main source However, functions SM in Fas-mediated apoptosis have yet be clearly defined, responsible genes not been identified. After cloning gene for synthesis, SMS1,...

10.1084/jem.20041685 article EN The Journal of Experimental Medicine 2005-07-11

Vitamin D3 treatment of the human promyelocytic cell line, HL-60, is accompanied by an increase in phorbol ester receptor number (Martell, R. E., Simpson, U., and Taylor, J. M. (1987) Biol. Chem. 262, 5570-5575). In this study, mechanism significance vitamin D3-induced changes protein kinase C levels were investigated. Treatment HL-60 cells with 1,25-dihydroxyvitamin (1,25-(OH)2D3) resulted a 2-3-fold dibutyrate binding at 24 h. This was 4.2-fold steady state mRNA for beta isoenzyme 3.8-fold...

10.1016/s0021-9258(19)39986-7 article EN cc-by Journal of Biological Chemistry 1990-02-01

Caspase-3 was cloned from zebrafish embryos and its properties were characterized to identify the biological implications of caspase in embryogenesis apoptosis zebrafish, which is a model organism vertebrate developmental biology genetics. The predicted amino acid sequence, totalling 282 residues, consisted prodomain large small subunits. Phylogenetic analysis showed that member caspase-3 subfamily with approx. 60% identity Xenopus, chicken mammals. In addition, recombinant hydrolysed...

10.1042/0264-6021:3600039 article EN Biochemical Journal 2001-11-15

Adult T-cell leukemia (ATL) is associated with prior infection human virus type 1 (HTLV-1); however, the mechanism by which HTLV-1 causes adult has not been fully elucidated. Recently, a functional basic leucine zipper (bZIP) protein coded in minus strand of genome (HBZ) was identified. We report here novel isoform bZIP factor (HBZ), HBZ-SI, identified means reverse transcription-PCR (RT-PCR) conjunction 5' and 3' rapid amplification cDNA ends (RACE). HBZ-SI 206-amino-acid-long generated...

10.1128/jvi.80.5.2495-2505.2006 article EN Journal of Virology 2006-02-11

Multicentric Castleman's disease (MCD) is a polyclonal lymphoproliferative disorder that manifests as marked hyper-γ-globulinemia, severe inflammation, anemia, and thrombocytosis. Recently, Takai et al. reported new concept, TAFRO syndrome, named from thrombocytopenia, anasarca, fever, reticulin fibrosis, organomegaly. Furthermore, Kojima Japanese MCD cases with effusion thrombocytopenia (Castleman-Kojima disease). Here, we report two of associated pleural effusion, ascites, discuss the...

10.3960/jslrt.53.79 article EN Journal of Clinical and Experimental Hematopathology 2013-01-01

Sodium nitroprusside (SNP), a NO donor, has been recognized as an inducer of apoptosis in various cell lines. Here, we demonstrated the intracellular formation ceramide, lipid signal mediator, SNP-induced human leukemia HL-60 cells and investigated mechanisms ceramide generation. The levels increased to, at most, 160% control level time- dose-dependent manner when were treated with 1 mm SNP. SNP also decreased sphingomyelin to ∼70% magnesium-dependent neutral sphingomyelinase (N-SMase)...

10.1074/jbc.274.15.10654 article EN cc-by Journal of Biological Chemistry 1999-04-01
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