A5042052859- Genomics, phytochemicals, and oxidative stress
- Antioxidant Activity and Oxidative Stress
- Inflammatory mediators and NSAID effects
- Cardiac Imaging and Diagnostics
- Peroxisome Proliferator-Activated Receptors
- Microbial Natural Products and Biosynthesis
- Free Radicals and Antioxidants
- Mitochondrial Function and Pathology
- Microbial metabolism and enzyme function
- Advanced Glycation End Products research
- Glutathione Transferases and Polymorphisms
- Monoclonal and Polyclonal Antibodies Research
- Eicosanoids and Hypertension Pharmacology
- Acute Myocardial Infarction Research
- Coronary Interventions and Diagnostics
- Cardiovascular Function and Risk Factors
- Redox biology and oxidative stress
- Marine Sponges and Natural Products
- DNA Repair Mechanisms
- Pancreatic function and diabetes
- Protein purification and stability
- Peptidase Inhibition and Analysis
- Biochemical Analysis and Sensing Techniques
- Atherosclerosis and Cardiovascular Diseases
- DNA and Nucleic Acid Chemistry
Nagoya University
2016-2025
Tokushima University Hospital
2014-2024
Ishikawa Prefectural Central Hospital
2023
Toyota Memorial Hospital
2023
The Jikei University Hospital
2015-2022
Jikei University School of Medicine
1996-2021
Tokai National Higher Education and Research System
2021
Tottori University
2021
Toyokawa City Hospital
2021
Tokyo University of Agriculture and Technology
2014-2021
The Keap1-Nrf2 system is the major regulatory pathway of cytoprotective gene expression against oxidative and/or electrophilic stresses. Keap1 acts as a stress sensor protein in this system. While constitutively suppresses Nrf2 activity under unstressed conditions, oxidants or electrophiles provoke repression activity, inducing activation. However, precise molecular mechanisms behind liberation from presence remain to be elucidated. We hypothesized that and stresses induce nuclear...
Activated macrophages express high levels of Nrf2, a transcription factor that positively regulates the gene expression antioxidant and detoxication enzymes. In this study, we examined how Nrf2 contributes to anti-inflammatory process. As model system acute inflammation, administered carrageenan induce pleurisy found in Nrf2-deficient mice, tissue invasion by neutrophils persisted during inflammation recruitment was delayed. Using an antibody against 15-deoxy-Delta(12,14)-prostaglandin J(2)...
Prostaglandin D<sub>2</sub>(PGD<sub>2</sub>), a major cyclooxygenase product in variety of tissues, readily undergoes dehydration to yield the cyclopentenone-type PGs J<sub>2</sub> series, such as 15-deoxy-Δ<sup>12,14</sup>-PGJ<sub>2</sub> (15d-PGJ<sub>2</sub>), which have been suggested exert anti-inflammatory effects <i>in vivo</i>. Meanwhile, mechanism these is not well understood and natural site extent its production<i>in vivo</i> remain unclear. In present study, we raised monoclonal...
Purified Escherichia coli recA protein catalyzed ATP-dependent pairing of superhelical DNA and homologous single-stranded fragments. The product the reaction: (i) was retained by nitrocellulose filters in 1.5 M NaCl/0.15 Na citrate at pH 7, (ii) dissociated 12.3 but not heating 55 degrees C for 4 min or treatment with 0.2% sodium dodecyl sulfate proteinase K, (iii) contained covalently closed circular double-stranded (form I DNA), (iv) fragments associated replicative form (RF) DNA, (v) a...
The Keap1-Nrf2 system plays a central role in the oxidative stress response; however, identity of reactive oxygen species sensor within Keap1 remains poorly understood. Here, we show that mutant lacking 11 cysteine residues retains ability to target Nrf2 for degradation, but it is unable respond cysteine-reactive inducers. Of mutated residues, find 4 (Cys226/613/622/624) are important sensing hydrogen peroxide. Our analyses multiple mice lines, complemented by MEFs expressing series mutants,...
AbstractTRPA1 is a member of the transient receptor potential (TRP) cation channel family, and predominantly expressed in nociceptive neurons dorsal root ganglia (DRG) trigeminal ganglia. Activation TRPA1 by environmental irritants such as mustard oil, allicin, acrolein causes acute pain. However, endogenous ligands that directly activate remain elusive inflammation. Here, we show variety inflammatory mediators (15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), nitric oxide (NO), hydrogen...
recA protein, which is essential for general genetic recombination in Escherichia coli, promotes the homologous pairing of single-stranded DNA with double-stranded to form a D loop. The amount protein required reaction was directly proportional single stranded and unaffected by similar variations DNA. ATP analog, adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S), not rapidly hydrolyzed blocked formation loops but promoted stable complexes These complexes, turn, bound or heterologous...
Prostaglandin D 2 (PGD ), a major cyclooxygenase product in variety of tissues and cells, readily undergoes dehydration to yield the bioactive cyclopentenone-type PGs J -series, such as 15-deoxy-Δ 12,14 -PGJ (15d-PGJ ). The observation that level 15d-PGJ increased tissue cells from patients with sporadic amyotrophic lateral sclerosis suggested formation may be closely associated neuronal cell death during chronic inflammatory processes. In vitro experiments using SH-SY5Y human neuroblastoma...
Prostaglandin (PG) D2, a major cyclooxygenase product in variety of tissues and cells, readily undergoes dehydration to yield the bioactive cyclopentenone-type PGs J2 series, such as 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2). We have shown previously that 15d-PGJ2 is potent electrophile causes intracellular oxidative stress redox alteration human neuroblastoma SH-SY5Y cells. In present study, based on observation electrophilic center was involved pro-oxidant effect, we investigated role thioredoxin 1...
Ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one], a seleno-organic compound showing glutathione peroxidase-like activity, is one of the promising synthetic antioxidants. In present study, we investigated electrophilic potential this antioxidant and established mechanism cysteine-targeted oxidation protein. addition, using ebselen as an probe, characterized cysteine residues required for posttranslational modification into electrophile sensor protein in phase 2 detoxification response....
Escherichia coli single-strand binding protein (SSB) or phage T4 gene 32 reduced the amount of recA required to catalyze formation D loops from double-stranded DNA and homologous single-stranded fragments. Neither SSB nor alone catalyzed loops, excessive amounts either protein, that were sufficient saturate single strands, inhibited completely. Both stimulatory activity inhibitory resisted boiling, which is consistent with known thermal stability SSB, whereas was inactivated by heating. The...
Abstract Human serum albumin (HSA) is the most abundant protein, contributing to maintenance of redox balance in extracellular fluids. One single free cysteine residue at position 34 believed be a target oxidation. However, molecular details and functions oxidized HSAs remain obscure. Here we analyzed samples from normal subjects hyperlipidemia patients observed an enhanced S -thiolation HSA as compared control individuals. Both homocysteine were identified low weight thiols bound HSAs....
Sterol regulatory element-binding proteins (SREBPs) are the key transcription factors that modulate lipid biosynthesis. SREBPs synthesized as endoplasmic reticulum-bound precursors require proteolytic activation in Golgi apparatus. The stability and maturation of precursor depend on their binding to SREBP cleavage-activating protein (SCAP), which escorts SCAP-SREBP complex In this study, we identified heat shock (HSP) 90 a novel regulator binds stabilizes SCAP-SREBP. HepG2 cells, HSP90...
Most triacylglycerol-lowering fibrates have been developed in the 1960s-1980s before their molecular target, peroxisome proliferator-activated receptor alpha (PPARα), was identified. Twenty-one ligand-bound PPARα structures deposited Protein Data Bank since 2001; however, binding modes of and physiological ligands remain unknown. Here we show thirty-four X-ray crystallographic ligand-binding domain, which are composed a "Center" four "Arm" regions, complexes with five endogenous fatty acids,...
A proteomic approach was used to identify 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) protein targets in human neuroblastoma SH-SY5Y cells. By using biotinylated 15d-PGJ2, β-actin found as the major adducted protein; at least 12 proteins were also identified minor biotin-positive spots, falling different functional classes, including glycolytic enzymes (enolase and lactate dehydrogenase), redox (biliverdin reductase), a eukaryotic regulatory (14-3-3γ). 15d-PGJ2 induced marked morphological...
trans-2-Nonenal is an unsaturated aldehyde with unpleasant greasy and grassy odor endogenously generated during the peroxidation of polyunsaturated fatty acids. 2-Nonenal covalently modified human serum albumin through a reaction in which preferentially reacted lysine residues. Modified proteins were immunogenic, specific monoclonal antibody (mAb) 27Q4 that cross-reacted protein 2-nonenal was raised from mouse. To verify presence protein-bound vivo, mAb against 2-nonenal-modified keyhole...
Because angiogenesis is essential for tumor growth and metastasis, the development of antiangiogenic agents an urgent issue in cancer treatment. Zerumbone, a component subtropical ginger, has been shown to exhibit anticancer activities various cells; however, little known about its biological mechanisms against pancreatic (PaCa). Here, we evaluated effects zerumbone on PaCa angiogenesis.The cytotoxicity was measured using premix WST-1 cell proliferation assays. The influence angiogenic...
Abstract Pyrroloquinoline quinone (PQQ), a redox-active o -quinone, is an important nutrient involved in numerous physiological and biochemical processes mammals. Despite such beneficial functions, the underlying molecular mechanisms remain to be established. In present study, using PQQ-immobilized Sepharose beads as probe, we examined presence of protein(s) that are capable binding PQQ mouse NIH/3T3 fibroblasts identified five cellular proteins, including l -lactate dehydrogenase (LDH) A...
Toll-like receptors (TLRs) play a key role in linking pathogen recognition with the induction of innate immunity. They have been implicated pathogenesis chronic inflammatory diseases, representing potential targets for prevention/treatment. Vegetable-rich diets are associated reduced risk several disorders. In present study, based on an extensive screening vegetable extracts TLR-inhibiting activity HEK293 cells co-expressing TLR NF-κB reporter gene, we found cabbage and onion to be richest...