A5048599186- Peptidase Inhibition and Analysis
- Advanced Proteomics Techniques and Applications
- 14-3-3 protein interactions
- Ovarian cancer diagnosis and treatment
- Amino Acid Enzymes and Metabolism
- Drug-Induced Hepatotoxicity and Protection
- Nitric Oxide and Endothelin Effects
- Tryptophan and brain disorders
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Endometriosis Research and Treatment
- GDF15 and Related Biomarkers
- Ubiquitin and proteasome pathways
- Enzyme Structure and Function
- Renal Diseases and Glomerulopathies
- Prostate Cancer Treatment and Research
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Long-Term Effects of COVID-19
- Circular RNAs in diseases
- Chromatin Remodeling and Cancer
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Cancer Mechanisms and Therapy
- Genomics and Phylogenetic Studies
- ATP Synthase and ATPases Research
- Pharmacogenetics and Drug Metabolism
National Institute of Health Sciences
2018-2025
National Institute of Infectious Diseases
2024
Yokohama City University
2008-2021
Yokohama City University Medical Center
2013-2018
Kansai University
2003-2009
Kyoto Prefectural University of Medicine
2005-2007
New ubiquitin ligase (E3) ligands are crucial for developing proteolysis-targeting chimeras (PROTACs) to induce the degradation of a target protein. In this study, we developed PROTAC using antipsychotic drug clozapine as new E3 ligand. First, targeting model HaloTag protein (Halo-PEG-Clozapine) was synthesized, and induced HaloTag-fused in cell culture system. Another cancer therapeutic estrogen receptor α (ERα) (Tamoxifen-PEG-Clozapine) synthesized ERα MCF-7 breast cells. Experiments with...
Of all of the epithelial ovarian cancers (EOC), clear cell adenocarcinoma (CCA) has worst clinical prognosis. Furthermore, conventional EOC biomarker CA125 is more often negative in CCA than other subtypes EOC. This study sought to discover a new diagnostic that would allow reliable detection CCA. Using mass spectrometry, we compared proteins conditioned media from lines derived and types We identified 30 extracellular or released specifically present CCA-derived lines. Bioinformatics...
The yeast (Saccharomyces cerevisiae) 26S proteasome consists of the 19S regulatory particle (19S RP) and 20S subunits. We detected comprehensively co- post-translational modifications these subunits using proteomic techniques. First, MS/MS, we investigated N-terminal three RP subunits, Rpt1, Rpn13, Rpn15, which had been unclear, found that N-terminus Rpt1 is not modified, whereas Rpn13 Rpn15 acetylated. Second, identified a total 33 Ser/Thr phosphorylation sites in 15 proteasome. data...
Involvement of reactive oxygen species (ROS) has been suggested in the development psychiatric disorders. NOX1 is a nonphagocytic form NADPH oxidase whose expression nervous system negligible compared with other NOX isoforms. However, NOX1-derived ROS increase inflammatory pain and tolerance to opioid analgesia. To clarify role brain, we examined depressive-like behaviors mice deficient Nox1 ( −/Y ). Depressive-like induced by chronic social defeat stress or administration corticosterone...
We previously reported the successful induction and completion of mouse spermatogenesis by culturing neonatal testis tissues. The culture medium consisted α-minimum essential (α-MEM), supplemented with Knockout serum replacement (KSR) or AlbuMAX, neither which were defined chemically. In this study, we formulated a chemically (CDM) that can induce under organ conditions. It was found bovine albumin (BSA) purified through three different procedures had effects on spermatogenesis. also...
Tissue factor pathway inhibitor 2 (TFPI2) is a novel serum biomarker that discriminates ovarian clear cell carcinoma (CCC) from borderline tumors (BOTs) and non-clear epithelial cancers (EOCs). Here, we examined the performance of TFPI2 for preoperative diagnosis CCC.Serum samples were obtained preoperatively patients with masses, who needed surgical treatment at five hospitals in Japan. The diagnostic powers cancer antigen 125 (CA125) levels to discriminate CCC BOTs, other EOCs, benign...
NADPH oxidase is the major source of superoxide production in cardiovascular tissues. We and others reported that PG (prostaglandin) F2α, PDGF (platelet-derived growth factor) angiotensin II cause hypertrophy vascular smooth muscle cells by induction NOX1 (NADPH 1), a catalytic subunit oxidase. found DPI (diphenylene iodonium), an inhibitor flavoproteins, including itself, almost completely suppressed mRNA PGF2α or rat cell line, A7r5. Exploration into site action using various inhibitors...
There is currently no reliable serum biomarker for ovarian clear cell carcinoma (CCC), a highly lethal histological subtype of epithelial cancer (EOC). Previously, using proteome-based approach, we identified tissue factor pathway inhibitor 2 (TFPI2) as candidate CCC. In this study, sought to evaluate the clinical diagnostic performance TFPI2 in preoperative prediction CCC.Serum levels were measured samples from retrospective training set consisting patients with benign and borderline...
Abstract Aim Tissue factor pathway inhibitor 2 (TFPI2) is a preoperative biomarker that was developed to discriminate ovarian benign tumors from cancer and covered by health insurance in Japan. The purpose of this study evaluate how the TFPI2 changes after treatment. Methods Serum levels (cut off 191 pg/mL) CA125 35 U/mL) before primary debulking surgery patients with malignant were evaluated among recurrent nonrecurrent cases, respectively. Results A total 46 cases analyzed, including 11...
Diffuse alveolar damage (DAD) is a pathological hallmark of severe interstitial lung diseases, such as acute respiratory distress syndrome (ARDS), and linked to poor prognosis. Previously, we identified 14–3–3σ/stratifin (SFN) serum biomarker candidate for diagnosing DAD. To clarify the time-dependent relationship between SFN expression DAD, here investigated molecular changes in serum, bronchoalveolar lavage fluid (BALF), tissue an oleic acid (OA)-induced ARDS rat model. Acute edema was...
Clioquinol has been thought of as the causative drug subacute myelo-optic neuropathy (SMON). The underlying mechanisms clioquinol toxicity, however, have not elucidated in detail. Here, we revealed that (20 μm) suppressed expression SCO1 and SCO2 copper chaperones for mitochondrial respiratory chain Complex IV (cytochrome c oxidase) SH-SY5Y neuroblastoma cells. assembly components activity were clioquinol-treated (10-50 decreased cellular ATP levels glucose-free media. induced OMA1...
The establishment of epithelial polarity is tightly linked to the dramatic reorganization microtubules (MTs) from a radial array vertical alignment non-centrosomal MT bundles along lateral membrane and meshwork under apical basal membranes. However, little known about underlying molecular mechanism this polarity-dependent remodeling. evolutionarily conserved cell polarity-regulating kinase PAR-1, whose activity essential for maintaining dynamic state MTs, plays indispensable roles promote...
Among the various histopathological patterns of drug-induced interstitial lung disease (DILD), diffuse alveolar damage (DAD) is associated with poor prognosis. However, there no reliable biomarker for its accurate diagnosis. Here, we show stratifin/14-3-3σ (SFN) as a candidate found in proteomic analysis. The study includes two independent cohorts (including totally 26 patients DAD) and controls (total 432 samples). SFN specifically elevated DILD DAD, superior to known biomarkers, KL-6 SP-D,...
Glycosylphosphatidylinositol (GPI) anchoring is a post-translational modification widely observed among eukaryotic membrane proteins. GPI anchors are attached to proteins via the carboxy-terminus in outer leaflet of cell membrane, where GPI-anchored (GPI-APs) perform important functions as coreceptors and enzymes. Precursors GPI-APs (Pre-GPI-APs) contain C-terminal hydrophobic sequence that involved cleavage signal from protein addition anchor by transamidase complex. In order confirm given...
Elucidating the androgen-independent growth mechanism is critical for developing effective treatment strategies to combat prostate cancer. We performed a comparative phosphoproteome analysis using cancer cell line, LNCaP, and an LNCaP-derived LNCaP-AI, identify phosphoproteins involved in this mechanism. quantitative comparisons of phosphopeptide levels tryptic digests protein extracts from these lines MS. found that 69 phosphopeptides 66 proteins significantly differed between LNCaP...
Abstract Drug-induced interstitial lung disease (DILD) occurs when drug exposure causes inflammation of the interstitium. DILD can be caused by different types drugs, and some patterns results in a high mortality rate; hence, poses serious problem clinical practice as well development, strategies to diagnose distinguish from other diseases are necessary. We aimed identify novel biomarkers for performing lipidomics analysis on plasma samples patients with acute recovery phase DILD. Having...
Abdominal aortic aneurysm (AAA) is a life-threatening disease, and no disease-specific circulating biomarkers for AAA screening are currently available. We have identified smooth muscle cell (SMC)-specific biomarker AAA. cultured aneurysmal tunica media that were collected from eight patients undergoing elective open-repair surgeries. Secreted proteins in culture medium subjected to liquid chromatography/tandem mass spectrometry. Myosin heavy chain 11 (myosin-11) was as SMC-specific protein...
A psychrophilic bacterium, Cytophaga sp. strain KUC-1, that abundantly produces a NAD(+)-dependent L-threonine dehydrogenase was isolated from Antarctic seawater, and the enzyme purified. The molecular weight of estimated to be 139,000, subunit determined 35,000. is homotetramer. Atomic absorption analysis showed contains no metals. In these respects, distinct other dehydrogenases have thus far been studied. L-Threonine DL-threo-3-hydroxynorvaline were substrates, NAD(+) some its analogs...
NADPH oxidase is implicated in the pathogenesis of various cardiovascular disorders. In vascular smooth muscle cells (VSMC), expression NOX1 (NADPH 1), a catalytic subunit oxidase, low and induced upon stimulation by vasoactive factors, while it abundantly expressed colon epithelial cells. To clarify regulatory mechanisms underlying such cell-specific expression, upstream regions directing transcription gene were explored. P53LMACO1 cells, cell line originated from mouse VSMCs, two novel...
NADPH oxidase is a major source of the superoxide produced in cardiovascular tissues. Expression NOX1, catalytic subunit oxidase, induced by various vasoactive factors, including angiotensin II, prostaglandin (PG) F 2α and platelet‐derived growth factor (PDGF). To clarify molecular basis this transcriptional activation, we delineated promoter region NOX1 gene. RT‐PCR 5′‐rapid amplification cDNA ends‐based analyses revealed novel 5′‐terminal exon rat gene located approximately 28 kb upstream...
Protein phosphorylation is one of the major factors involved in tumor progression and malignancy. We performed exploratory studies aimed at identifying phosphoproteins characteristic to cell lines derived from ovarian clear adenocarcinoma (CCA), a highly malignant type cancer. Comparative phosphoproteome analysis revealed that phosphopeptides five SWI/SNF chromatin remodeling/tumor suppressor components, including ARID1A BRG1, were significantly down-regulated CCA cells. then quantitatively...