A5059002532- DNA Repair Mechanisms
- Mitochondrial Function and Pathology
- Cancer-related Molecular Pathways
- Alzheimer's disease research and treatments
- Genomics, phytochemicals, and oxidative stress
- RNA modifications and cancer
- Metabolism and Genetic Disorders
- Skin Protection and Aging
- Immune Response and Inflammation
- Epigenetics and DNA Methylation
- Genetic factors in colorectal cancer
- Neurological Disease Mechanisms and Treatments
- Pharmacological Effects and Toxicity Studies
- Photodynamic Therapy Research Studies
- Coenzyme Q10 studies and effects
- Diabetes and associated disorders
- Cardiomyopathy and Myosin Studies
- PARP inhibition in cancer therapy
- Cholinesterase and Neurodegenerative Diseases
- Cellular transport and secretion
- FOXO transcription factor regulation
- Proteoglycans and glycosaminoglycans research
- Nerve injury and regeneration
- Diet, Metabolism, and Disease
- Cancer Genomics and Diagnostics
Kyushu University
2010-2025
Kurashiki Central Hospital
2024
Fukuoka University
1997-2024
Fukuoka Dental College
2019-2022
ID Genomics (United States)
2016
St. Petersburg Institute of Bioregulation and Gerontology
2010-2013
Case Western Reserve University
1995
Diabetes mellitus (DM) is considered to be a risk factor for dementia including Alzheimer's disease (AD). However, the molecular mechanism underlying this not well understood. We examined gene expression profiles in postmortem human brains donated Hisayama study. Three-way analysis of variance microarray data from frontal cortex, temporal and hippocampus was performed with presence/absence AD vascular dementia, sex, as factors. Comparative analyses changes patients mouse model were also...
Synthetic sickness/lethality (SSL) can be exploited to develop therapeutic strategies for cancer. Deficiencies in the tumor suppressor proteins MLH1 and MSH2 have been implicated Here we demonstrate that deficiency is SSL with inhibition of DNA polymerase POLB, whereas POLG inhibition. Both SSLs led accumulation 8-oxoG oxidative lesions. MSH2/POLB caused nuclear accumulation, MLH1/POLG a rise mitochondrial levels. were rescued by silencing adenine glycosylase MUTYH, suggesting lethality...
8-Oxoguanine (8-oxoG), a common DNA lesion caused by reactive oxygen species, is associated with carcinogenesis and neurodegeneration. Although the mechanism which 8-oxoG causes well understood, it neurodegeneration unknown. Here, we report that triggered MUTYH-mediated excision repair of 8-oxoG-paired adenine. Mutant mice lacking 8-oxo-2'-deoxyguanosine triphosphate-depleting (8-oxo-dGTP-depleting) MTH1 and/or 8-oxoG-excising OGG1 exhibited severe striatal neurodegeneration, whereas mutant...
Abstract Oxidative stress and mitochondrial dysfunction are implicated in aging-related neurodegenerative disorders. 8-Oxoguanine (8-oxoG), a common oxidised base lesion, is often highly accumulated brains from patients with MTH1 hydrolyses 8-oxo-2′-deoxyguanosine triphosphate (8-oxo-dGTP) to 8-oxo-dGMP pyrophosphate nucleotide pools, while OGG1 excises 8-oxoG paired cytosine DNA, thereby minimising the accumulation of DNA. Mth1/Ogg1 -double knockout (TO-DKO) mice susceptible...
Abstract In the mitochondria-mediated vicious cycle of Alzheimer’s disease (AD), intracellular amyloid β (Aβ) induces mitochondrial dysfunction and reactive oxygen species, which further accelerate Aβ accumulation. This is thought to play a pivotal role in development AD, although molecular mechanism remains unclear. Here, we examined effects human transcriptional factor A (hTFAM) on pathology mouse model AD (3xTg-AD), because TFAM known protect mitochondria from oxidative stress through...
8-Oxoguanine (8-oxoG), a major oxidative base lesion, is highly accumulated in Alzheimer's disease (AD) brains during the pathogenic process. MTH1 hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, thereby avoiding 8-oxo-dG incorporation into DNA. 8-OxoG DNA glycosylase-1 (OGG1) excises 8-oxoG paired with cytosine DNA, minimizing accumulation Levels of and OGG1 are significantly reduced sporadic AD cases. To understand how genome involved pathogenesis, we established an mouse model knockout Mth1 Ogg1...
Missense mutations in the TP53 (p53) gene have been linked to malignant progression. However, our in-silico analyses reveal that hepatocellular carcinoma (HCC) patients with mutant p53 (mutp53) better overall survival compared those p53-null (p53null) HCC, unlike other cancer types. Given historical use of sorafenib (SOR) monotherapy for advanced we hypothesize mutp53 increases sensitivity SOR, a multikinase inhibitor induces endoplasmic reticulum (ER) stress. Here show inhibits stress...
p53-regulated caspase-independent cell death has been implicated in suppression of tumorigenesis, however, the regulating mechanisms are poorly understood. We previously reported that 8-oxoguanine (8-oxoG) accumulation nuclear DNA (nDNA) and mitochondrial triggers two distinct through buildup single-strand breaks by MutY homolog (MUTYH), an adenine glycosylase. One pathway depends on poly-ADP-ribose polymerase (PARP) other calpains. Deficiency MUTYH causes MUTYH-associated familial...
Retinitis pigmentosa (RP) is a genetically heterogenous group of inherited retinal degenerative diseases resulting from photoreceptor cell death and affecting >1 million persons globally. Although oxidative stress has been implicated in the pathogenesis RP, mechanisms by which mediates are largely unknown. Here, we show that oxidation nucleic acids key component initiation death-signaling pathways rd10 mice, model RP. Accumulation 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) increased...
HNK-1 carbohydrate antigen in an epitope expressed commonly many cell surface adhesion and recognition molecules the nervous system. We purified characterized from rat brain a novel phosphatidylinositol (PI)-anchored 150-kD glycoprotein belonging to family. The molecule (PI-GP150) was detected by combination of PI-specific phospholipase C treatment membranes Western blot analysis with mAb HNK-1. HNK-1-positive PI-GP150 PI-PLC-released materials three successive chromatographies (Sephacryl...
NCAM in its high polysialic acid (PSA) form is expressed on chick hindlimb motoneurons during their growth, and then decreases at about the time that synaptogenesis completed. In order to characterize this regulation cell molecular level, present studies use ciliary ganglion (CG) system, which constitutes a homogeneous developmentally synchronized population of can be used for vitro studies. Levels PSA CG were evaluated both by SDS-PAGE immunoblot analysis total pulse radiolabeling newly...
Oxidative stress plays a pivotal role in the differentiation and proliferation of cells programmed cell death. However, studies on oxidative have mainly employed detection reactive oxygen species (ROS) during or generated by ROS inducers. Therefore, it is difficult to clarify significance endogenous production human cells. We developed system control intracellular level initial stage iPS By introducing specific substitution (I69E) into SDHC protein, component mitochondrial respiratory chain...
Reactive oxygen species (ROS) generated during cellular respiration oxidize various constituents, which cause carcinogenesis. Because most studies on the role of ROS in carcinogenesis have mainly been performed using tumor-derived cell lines, harbor types mutation, it has difficult to determine molecular details that lead cancer formation. To overcome this difficulty, we established human-induced pluripotent stem lines intracellular levels are controlled at differentiation stages by...