PubMed Health⌕ Search

Biomedical subjects

Yasuo Kagawa

Publications and source records attributed to Yasuo Kagawa.

At least 19 recordsLinked to original sources
PubMed2006

Mitochondrial functions and estrogen receptor-dependent nuclear translocation of pleiotropic human prohibitin 2.

Proteins with multiple cellular functions provide biological diversity to eukaryotic cells. In the current studies, we identified the mitochondrial functions of human prohibitin 2 (PHB2), which was initially identified as a repressor of estrogen-dependent transcriptional activity. The mitochondrial complex of PHB2 consists of PHB1, voltage-dependent anion channel 2, adenine nucleotide translocator 2, and the anti-apoptotic Hax-1, which is a novel binding partner for PHB2. RNA interference-mediated knockdown of PHB2 in HeLa cells resulted in caspase-dependent apoptosis through down-regulation of Hax-1 and fragmentation of mitochondria. We also found that, although PHB2 is predominantly expressed in the mitochondria of HeLa cells, it translocates to nucleus in the presence of estrogen receptor alpha and estradiol. Here, we first demonstrated the roles of mammalian PHB2 in mitochondria and the molecular mechanism of its nuclear targeting and showed that PHB2 is a possible molecule directly coupling nuclear-mitochondrial interaction.

Active Transport, Cell Nucleus↗
PubMed2006

Investigation of oxidative stress and dietary habits in Mongolian people, compared to Japanese people.

BACKGROUND: The average life span of Mongolians is 62 years for males and 69 years for females. This life span is about 16 years shorter than that of Japanese. Mongolian people generally eat meat, fat and diary products but less vegetables or fruit. Thus, we investigated the state of oxidative stress and dietary habits of Mongolians. METHODS: The investigation was performed in Murun city in the northwest area of Mongolia. A total of 164 healthy subjects (24-66 y) were enrolled. As a marker of reactive oxygen species, the levels of reactive oxygen metabolites (ROM) were measured using the d-ROM test. Interviews about dietary habits were performed using the Food Frequency Questionnaire established by the Kagawa Nutrition University. RESULTS: ROM levels were 429.7 +/- 95.2 Carr U for Murun subjects, whereas Japanese people (n = 220, 21-98 y) showed 335.3 +/- 59.8 (p < 0.001). The levels of serum malondialdehyde-modified low-density lipoprotein-cholesterol and urinary 8-hydroxydeoxyguanosine were also high. ROM levels correlated with body fat ratio and inversely correlated with handgrip strength. Handgrip strength in the subjects over 45 years decreased more rapidly than that of age-matched Japanese. Murun subjects ate larger amounts of meat, fat, milk and flour and dairy products than Japanese, but less vegetables or fruit. Serum vitamin A and E levels were the same as Japanese references, but vitamin C levels were lower. CONCLUSION: Murun subjects may be in high oxidative stress, which may have a relationship with early ageing and several diseases, ultimately resulting in their short life span. In order to increase antioxidant capacity and suppress overproduction of ROM, antioxidant food intake is recommended.

Journal Article↗
PubMed2005

Serotonin transporter polymorphisms affect human blood glucose control.

We measured the effect of nutritional intervention on clinical data, including fasting blood glucose (FBG), and their association with polymorphisms of the serotonin transporter-linked polymorphic region (5-HTTLPR) which might affect adherence. Enrolled in the intervention program were 264 Japanese women not on medication for diabetes, hypercholesterolemia or hypertension. The 5-HTTLPR allele (S and L) frequencies among the subjects differed markedly from those of Caucasians: SS (n = 183), LS (n = 69), and LL (n = 12). The decrease in FBG (DeltaFBG) from the beginning to the end of the program (11 weeks; short-term study), and DeltaFBG from the beginning to a follow-up check performed between 2002 and 2004 (average of 23 years later; long-term study) was calculated. The SS homozygotes of 5-HTTLPR showed larger DeltaFBG (P = 0.01 and P < 0.0001 in the short- and long-term studies, respectively) than DeltaFBG with other genotypes.

Adult↗
PubMed2005

High prevalence of hepatitis delta virus infection detectable by enzyme immunoassay among apparently healthy individuals in Mongolia.

A previous study revealed a high prevalence of hepatitis B surface antigen (HBsAg) and hepatitis delta virus (HDV) RNA among 249 apparently healthy individuals (mean+/-standard deviation age, 48.4+/-13.9 years; 126 males and 123 females) in Ulaanbaatar, Mongolia. To investigate further the prevalence of HDV infection there, the same serum samples obtained from the cohort were tested for the presence of immunoglobulin G (IgG) class antibody to HDV (anti-HDV) by a newly developed enzyme-linked immunosorbent assay using recombinant hepatitis delta antigen protein expressed in the pupae of silkworm as the antigen probe. Anti-HDV was detected in 42 persons (16.9%), among whom 22 (52.4%) were positive for HBsAg and 20 (47.6%) had detectable HDV RNA. Among 170 persons with anti-HBc in the absence of HBsAg, 20 (11.8%) tested positive for anti-HDV, and 1 of the 20 subjects was positive for HDV RNA. Of note, none of 55 anti-HBc-negative persons had anti-HDV, supporting the specificity of the anti-HDV assay. The optical density (OD) value of anti-HDV was significantly higher among HDV RNA-positive subjects (n=21) than among HDV RNA-negative subjects (n=21) (2.513+/-0.514 vs. 0.836+/-0.550, P<0.0001). The present study confirmed the extremely high prevalence of HDV infection in Mongolia, and identified a person who was positive for both anti-HDV and HDV RNA despite negativity for HBsAg and HBV DNA probably due to viral interference. The anti-HDV assay may be useful for further epidemiological studies on HDV infection in larger cohorts in urban and rural areas of Mongolia, where elucidation of the transmission route of HDV is required urgently.

Adult↗
PubMed2004

Accumulation of pathogenic DeltamtDNA induced deafness but not diabetic phenotypes in mito-mice.

Mito-mice carrying various proportions of deletion mutant mtDNA (DeltamtDNA) were generated by introduction of the DeltamtDNA from cultured cells into fertilized eggs of C57BL/6J (B6) strain mice. Great advantages of mito-mice are that they share exactly the same nuclear-genome background, and that their genetic variations are restricted to proportions of pathogenic DeltamtDNA. Since accumulation of DeltamtDNA to more than 75% induced respiration defects, the disease phenotypes observed exclusively in mito-mice carrying more than 75% DeltamtDNA should be due to accumulated DeltamtDNA. In this study, we focused on the expressions of hearing loss and diabetic phenotypes, since these common age-associated abnormalities have sometimes been reported to be inherited maternally and to be associated with pathogenic mutant mtDNAs. The results showed that accumulation of exogenously introduced DeltamtDNA was responsible for hearing loss, but not for expression of diabetic phenotypes in mito-mice.

Animals↗
PubMed2004

Gene-nutrient and gene-gene interactions of controlled folate intake by Japanese women.

Elevated serum total homocysteine (tHcy) levels are associated with increased risk for cardiovascular disease and dementia. The prevalence rates of homozygous mutants among Japanese women (n = 300) were 17.3%, 1.3%, 18.6%, and 5.3% for methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, reduced folate carrier (RFC-1) A80G, and methionine synthase (MS) A2756G, respectively. The tHcy value was significantly lower (p < 0.001) in young women with CC or CT of MTHFR than with TT (10.9+/-4.7 micromol/L) (n =250). Diversities of serum folate and tHcy in women with 23 combinations of different alleles at low folate intake converged to the highest (34.0+/-8.6 nmol/L) and lowest (7.6+/-1.5 micromol/L) levels, respectively, after folic acid (400 microg/day) supplementation. In the regression equation ( y= ax + b) of serum folate ( y nmol/L) plotted against mean folate intake ( x microg/day), the values of "a" were 0.032, 0.037, and 0.045 for individuals with CC, CT, and TT alleles, respectively, of MTHFR.

Adult↗
PubMed2004

Human DDB2 splicing variants are dominant negative inhibitors of UV-damaged DNA repair.

Damaged DNA-binding protein (DDB) is a heterodimer (DDB1 and DDB2), which is implicated in the repair of UV-irradiated DNA damage. Here we have identified four DDB2 variants from HeLa cells (D1-D4) that are generated by alternative splicing. Analysis of tissue distribution by RT-PCR indicates that D1 is the most highly expressed in human brain and heart. A DNA repair assay revealed that both D1 and D2 are dominant negative inhibitors. Electrophoresis mobility shift assays indicated that D1 and D2 are not part of the damaged DNA-protein complex. Co-immunoprecipitation studies show that DDB2-WT interacts with D1 and itself. Nuclear import of DDB1 was less induced by transfection with D1 than WT. Based on these results, D1 and D2 are dominant negative inhibitors of DNA repair, which is probably due to disruption of complex formation between DDB1 and DDB2-WT and of DDB1 nuclear import.

Base Sequence↗
PubMed2004

Mammalian D-aspartyl endopeptidase: a scavenger for noxious racemized proteins in aging.

The accumulation of D-isomers of aspartic acid (D-Asp) in proteins during aging has been implicated in the pathogenesis of Alzheimer's disease, cataracts, and arteriosclerosis. Here, we identified a specific lactacystin-sensitive endopeptidase that cleaves the D-Asp-containing protein and named it D-aspartyl endopeptidase (DAEP). DAEP has a multi-complex structure (MW: 600kDa) and is localized in the inner mitochondrial membrane of mouse and rabbit, but DAEP activity was not detected in Escherichia coli, Saccharomyces cerevisiae, and Caenorhabditis elegans. A specific inhibitor for DAEP was newly synthesized, and inhibited DAEP activity (IC(50), 3microM), a factor of 10 greater than lactacystin on DAEP. On the other hand, the inhibitor did not inhibit either the 20S or 26S proteasome.

Aging↗
PubMed2004

Biotin enhances ATP synthesis in pancreatic islets of the rat, resulting in reinforcement of glucose-induced insulin secretion.

Previous studies showed that biotin enhanced glucose-induced insulin secretion. Changes in the cytosolic ATP/ADP ratio in the pancreatic islets participate in the regulation of insulin secretion by glucose. In the present study we investigated whether biotin regulates the cytosolic ATP/ADP ratio in glucose-stimulated islets. When islets were stimulated with glucose plus biotin, the ATP/ADP ratio increased to approximately 160% of the ATP/ADP ratio in islets stimulated with glucose alone. The rate of glucose oxidation, assessed by CO(2) production, was also about 2-fold higher in islets treated with biotin. These increasing effects of biotin were proportional to the effects seen in insulin secretion. There are no previous reports of vitamins, such as biotin, directly affecting ATP synthesis. Our data indicate that biotin enhances ATP synthesis in islets following the increased rate of substrate oxidation in mitochondria and that, as a consequence of these events, glucose-induced insulin release is reinforced by biotin.

Adenosine Diphosphate↗
PubMed2004

Comparison of electrocardiogram findings and lifestyles between urbanized people and ger-living people in Ulaanbaatar, Mongolia.

In Ulaanbaatar, lifestyles differ between urbanized people (group A) and ger (tent)-living people (group B). Group A earn high annual incomes and live in houses or apartments. Group B (who had moved to Ulaanbaatar from nomadic areas) earn low incomes and live in narrow gers. In 2002, we investigated daily food intake, health status, and electrocardiogram (ECG) in these groups. In total, 256 subjects (group A, 142; group B, 114) were enrolled. Group A ate meat, vegetables, and fruits high enough by a Western style. Group B consumed meat but ate only small amounts of vegetables and fruits. They took a lot of fat, however, the serum lipid levels of them were not so high. The fat source as energy was plant oil for cooking rather than meat. Several abnormal ECG findings including left ventricular hypertrophy (LVH) were found in 32 (22.5%) of group A and 50 (43.9%) of group B (P < 0.001). LVH was also found more in group B than in group A. LVH in group A males was accompanied by high body weight (BW), hypertension, and high LDL-cholesterol, whereas LVH in group B males seemed to be related to an unbalanced diet, high salt intake, smoking, and some low socio-economic problems. In order to promote health condition, such risk factors should securely be eliminated from the lifestyles.

Adult↗
PubMed2004

Prevalence of diego blood group Dia antigen in Mongolians: comparison with that in Japanese.

The Diego blood group is composed of Di(a) and Di(b) antigens. Prevalence of the Di(a) antigen is known to be different among races. The Di(a) antigen is generally found in Oriental people. Thus, it is called a Mongoloid factor. In Japanese, the prevalence of this antigen is 8.78%. However, the prevalence in Mongolians had not previously been examined. In September of 2002, we determined this antigen among inhabitants of Ulaanbaatar. It was found in 24 of 242 subjects (9.92%). This prevalence approximates that in Japanese. The Rh blood group phenotypes also showed patterns similar to those in Japanese. These results are not contrary to the presumption that Mongolians and Japanese may have a common racial background.

Alleles↗
PubMed2004

High prevalence of antibodies to hepatitis A and E viruses and viremia of hepatitis B, C, and D viruses among apparently healthy populations in Mongolia.

The prevalence of infection with hepatitis A virus (HAV), HBV, HCV, HDV, and HEV was evaluated in 249 apparently healthy individuals, including 122 inhabitants in Ulaanbaatar, the capital city of Mongolia, and 127 age- and sex-matched members of nomadic tribes who lived around the capital city. Overall, hepatitis B surface antigen (HBsAg) was detected in 24 subjects (10%), of whom 22 (92%) had detectable HBV DNA. Surprisingly, HDV RNA was detectable in 20 (83%) of the 24 HBsAg-positive subjects. HCV-associated antibodies were detected in 41 (16%) and HCV RNA was detected in 36 (14%) subjects, none of whom was coinfected with HBV, indicating that HBV/HCV carriers account for one-fourth of this population. Antibodies to HAV and HEV were detected in 249 (100%) and 28 (11%) subjects, respectively. Of 22 HBV DNA-positive subjects, genotype D was detected in 21 subjects and genotype F was detected in 1 subject. All 20 HDV isolates recovered from HDV RNA-positive subjects segregated into genotype I, but these differed by 2.1 to 11.4% from each other in the 522- to 526-nucleotide sequence. Of 36 HCV RNA-positive samples, 35 (97%) were genotype 1b and 1 was genotype 2a. Reflecting an extremely high prevalence of hepatitis virus infections, there were no appreciable differences in the prevalence of hepatitis virus markers between the two studied populations with distinct living place and lifestyle. A nationwide epidemiological survey of hepatitis viruses should be conducted in an effort to prevent de novo infection with hepatitis viruses in Mongolia.

Adult↗
PubMed2003

Improvement in blood lipid levels by dietary sn-1,3-diacylglycerol in young women with variants of lipid transporters 54T-FABP2 and -493g-MTP.

UNLABELLED: In a double-blind parallel-group study, serum lipids and visceral fat/total fat ratio in young women (n=49) with variants of lipid transporters, i.e., fatty acid binding protein 2 (FABP2) and microsomal triglyceride transfer protein (MTP), were analyzed by substituting dietary triacylglycerol (TAG) with sn-1,3-diacylglycerol (DAG). All subjects, including some with the hyperlipidemia-prone genotypes Ala54Thr of FABP2 and c-493g of MTP, received DAG or TAG (20 g/day) for 8 weeks. Reductions of serum lipids from weeks 4 to 8 in FABP2-Ala54Thr heterozygotes and MTP -493g homozygotes were significantly different between the DAG and TAG groups (p<0.05, p<0.01). Visceral fat/total fat (%), as determined by computed tomography (CT), was lower in FABP2-Ala54Thr heterozygotes (p<0.05) of the DAG group. The apoCII/CIII ratio was higher in the DAG group than in the TAG group (p<0.01). Other variants of lipid metabolism, including peroxisome proliferator activated receptors (PPARs) alpha and gamma and SREBP cleavage-activating protein (SCAP), were only slightly affected by dietary DAG. CONCLUSION: improvement of serum lipid profiles and visceral fat/total fat ratio (CT) was potentiated by DAG intake in subjects with hyperlipidemia-prone genotypes (Ala54Thr heterozygotes of FABP2 and -493g homozygotes of MTP).

Adipose Tissue↗
PubMed2003

Differential sublocalization of the dynamin-related protein OPA1 isoforms in mitochondria.

OPA1 is a cause gene for autosomal dominant optic atrophy and possesses eight alternative splicing variants. Here, we identified two isoforms of OPA1 proteins in HeLa cells and examined their submitochondrial localization and complex formations. RT-PCR shows that HeLa cells mainly express isoforms 7 and 1 of OPA1. Since the third cleavage site is mainly utilized in HeLa cells, the predicted molecular masses of their processed proteins are consistent with the 93- and 88-kDa proteins. Biochemical examinations indicate that both of the OPA1 isoforms are present in the intermembrane space. Submitochondrial fractionation by sucrose density-gradient centrifugation shows that the 88-kDa protein predominantly associates with the mitochondrial outer membrane, on the contrary, the 93-kDa protein associates with the inner membrane. Gel filtration analysis indicates that they compose the different molecular mass complexes in mitochondria. These differences between two isoforms of OPA1 would suggest their crucial role involved in the mitochondrial membrane formation.

Alternative Splicing↗
PubMed2003

Association of alpha-subunits with nucleotide-modified beta-subunits induces asymmetry in the catalytic sites of the F1-ATPase alpha3beta3-hexamer.

The photoaffinity spin-labeled ATP analog, 2-N3-SL-adenosine triphosphate (ATP), was used to covalently modify isolated beta-subunits from F1-ATPase of the thermophilic bacterium PS3. Approximately 1.2 mol of the nucleotide analog bound to the isolated subunit in the dark. Irradiation leads to covalent incorporation of the nucleotide into the binding site. ESR spectra of the complex show a signal that is typical for protein-immobilized radicals. Addition of isolated alpha-subunits to the modified beta-subunits results in ESR spectra with two new signals indicative of two distinctly different environments of the spin-label, e.g., two distinctly different conformations of the catalytic sites. The relative ratio of the signals is approx 2:1 in favor of the more closed conformation. The data show for the first time that when nucleotides are bound to isolated beta-subunits, binding of alpha-subunits induces asymmetry in the catalytic sites even in the absence of the gamma-subunit.

Adenosine Diphosphate↗
PubMed2002

cDNA cloning and characterization of Drb1, a new member of RRM-type neural RNA-binding protein.

Neural RNA recognition motif (RRM)-type RNA-binding proteins play essential roles in neural development. To search for a new member of neural RRM-type RNA-binding protein, we screened rat cerebral expression library with polyclonal antibody against consensus RRM sequences. We have cloned and characterized a rat cDNA that belongs to RRM-type RNA-binding protein family, which we designate as drb1. Orthologs of drb1 exist in human and mouse. The predicted amino acid sequence reveals an open reading frame of 476 residues with a corresponding molecular mass of 53kDa and consists of four RNA-binding domains. drb1 gene is specifically expressed in fetal (E12, E16) rat brain and gradually reduced during development. In situ hybridization demonstrated neuron-specific signals in fetal rat brain. RNA-binding assay indicated that human Drb1 protein possesses binding preference on poly(C)RNA. These results indicate that Drb1 is a new member of neural RNA-binding proteins, which expresses under spatiotemporal control.

Amino Acid Sequence↗
PubMed2002

Single nucleotide polymorphisms of thrifty genes for energy metabolism: evolutionary origins and prospects for intervention to prevent obesity-related diseases.

The "thrifty" genotype and phenotype that save energy are detrimental to the health of people living in affluent societies. Individual differences in energy metabolism are caused primarily by single nucleotide polymorphisms (SNPs), some of which promote the development of obesity/type 2 diabetes mellitus. In this review, four major questions are addressed: (1) Why did regional differences in energy metabolism develop during evolution? (2) How do genes respond to starvation and affluence? (3) Which SNPs correspond to the hypothetical "thrifty genes"? (4) How can we cope with disease susceptibility caused by the "thrifty" SNPs? We examined mtDNA and genes for energy metabolism in people who live in several parts of Asia and the Pacific islands. We included 14 genes, and the SNP frequencies of PPAR gamma 2, LEPR, and UCP3-p and some other genes differ significantly between Mongoloids and Caucasoids. These differences in SNPs may have been caused by natural selection depending on the types of agriculture practiced in different regions. Interventions to counteract the adverse effects of "thrifty" SNPs have been partially effective.

Evolution, Molecular↗