Yasuo Kagawa - Academia.edu (original) (raw)

Papers by Yasuo Kagawa

Current Aging Sciencee, 2008

Proceedings of the Japan Academy, Series B, 2010

Journal of Biological Chemistry, 2000

Journal of Biochemistry

ATPase complexes were reconstituted from homologous and heterologous combinations of alpha, beta,... more ATPase complexes were reconstituted from homologous and heterologous combinations of alpha, beta, and gamma subunits of coupling factor ATPase TF1 of thermophilic bacterium PS3 and EF1 of Escherichia coli. TF1 and alpha beta gamma complex reconstituted from TF1 subunits were thermostable and activated by methanol, sodium dodecyl sulfate and anions and they were halophilic, whereas EF1 and its three-subunit complex did not show these properties. The hybrid ATPase alpha T beta T gamma E (complex of the alpha and beta subunits of TF1 and the gamma subunit of EF1) showed closely similar properties to TF1 except for thermostability, while alpha E beta E gamma T (alpha and beta from EF1 and gamma from TF1) had similar properties to EF1. These results suggest that alpha and/or beta is required for the properties of F1. The complex alpha E beta T gamma E showed similar properties to EF1 except for its optimum pH: this complex had a broad pH optimum at about pH 7, whereas EF1 had an optimum at pH 8.5. No hybrid complexes were thermostable, suggesting that all three subunits of TF1 are required for heat stability. These hybrids showed higher halophilicity than EF1, although they were less halophilic than TF1. The hybrid enzymes studied here are the first thermophilic-mesophilic hybrid enzymes obtained.

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Nihon rinsho. Japanese journal of clinical medicine, 2012

Lifestyle controls the circadian rhythms produced by clock genes and affects telomere length that... more Lifestyle controls the circadian rhythms produced by clock genes and affects telomere length that regulates healthspan. Biological clocks are classified into oscillatory (clock genes) and hourglass clocks (telomeres). Clock genes align behavioral and biochemical processes with the day/night cycle. Telomeres, the repeated series of DNA sequences that cap the ends of chromosomes, become shorter during cell division. Shortened telomeres have been documented in various pathological states in lifestyle-related diseases, such as atherosclerosis and diabetes. Human activity is driven by NADH and ATP produced from nutrients, and the resulting NAD and AMP play a predominant role in energy regulation. Caloric restriction and proper exercise increase both AMP and NAD, and extend the healthspan. SIRT1, the NAD-dependent deacetylase, attenuates telomere shortening, while PGC-1alpha, a master modulator of gene expression, is phosphorylated by AMP kinase and deacetylated by SIRT1. Prevention of li...

Nutrition & metabolism, 2006

The average life span of Mongolians is 62 years for males and 69 years for females. This life spa... more 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. 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. 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 l...

Transplantation, Jan 15, 1998

Cytokine profile is a key in understanding the mechanisms of allograft rejection. Cytokine expres... more Cytokine profile is a key in understanding the mechanisms of allograft rejection. Cytokine expression in the aqueous humor and the correlation between the aqueous humor cells and corneal infiltrating cells are not fully understood in corneal transplantation. Orthotopic mouse corneal transplantation was performed using BALB/c (H2d) mice as recipients, and C3H/He (H2k) and BALB/c mice as donors for allografts and isografts, respectively. Immunocytochemistry was performed on aqueous humor cells. Corneal graft was studied immunohistochemically. Cytokine gene expressions of the cells infiltrating the aqueous humor and corneal grafts were determined by the semiquantitative reverse transcription and polymerase chain reaction method. Interferon-gamma, interleukin (IL)-2, IL-4, and IL-10 were detected in the cells infiltrating the aqueous humor and corneal grafts at both the protein and gene expression levels. T helper 1 (Th1) cytokine expressions at the protein level, however, were consiste...

Transfusion and Apheresis Science, 2004

The Diego blood group is composed of Di(a) and Di(b) antigens. Prevalence of the Di(a) antigen is... more 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.

The Journal of General and Applied Microbiology, 1992

ABSTRACT

Structure, 1997

Background: F1-ATPase, an oligomeric assembly with subunit stoichiometry α3β3γδϵ, is the catalyti... more Background: F1-ATPase, an oligomeric assembly with subunit stoichiometry α3β3γδϵ, is the catalytic component of the ATP synthase complex, which plays a central role in energy transduction in bacteria, chloroplasts and mitochondria. The crystal structure of bovine mitochondrial F1-ATPase displays a marked asymmetry in the conformation and nucleotide content of the catalytic β subunits. The α3β3 subcomplex of F1-ATPase has been

Proceedings of the National Academy of Sciences, 1999

To determine whether pathogenic mutations in mtDNA are involved in phenotypic expression of Alzhe... more To determine whether pathogenic mutations in mtDNA are involved in phenotypic expression of Alzheimer's disease (AD), the transfer of mtDNA from elderly patients with AD into mtDNA-less (rho0) HeLa cells was carried out by fusion of platelets or synaptosomal fractions of autopsied brain tissues with rho0 HeLa cells. The results showed that mtDNA in postmortem brain tissue survives for a long time without degradation and could be rescued in rho0 HeLa cells. Next, the cybrid clones repopulated with exogenously imported mtDNA from patients with AD were used for examination of respiratory enzyme activity and transfer of mtDNA with the pathogenic mutations that induce mitochondrial dysfunction. The presence of the mutated mtDNA was restricted to brain tissues and their cybrid clones that formed with synaptosomes as mtDNA donors, whereas no cybrid clones that isolated with platelets as mtDNA donors had detectable mutated mtDNA. However, biochemical analyses showed that all cybrid clones with mtDNA imported from platelets or brain tissues of patients with AD restored mitochondrial respiration activity to almost the same levels as those of cybrid clones with mtDNA from age-matched normal controls, suggesting functional integrity of mtDNA in both platelets and brain tissues of elderly patients with AD. These observations warrant the reassessment of the conventional concept that the accumulation of pathogenic mutations in mtDNA throughout the aging process is responsible for the decrease of mitochondrial respiration capacity with age and with the development of age-associated neurodegenerative diseases.

Proceedings of the National Academy of Sciences, 1977

Purified dicyclohexylcarbodiimide-sensitive ATPase (TF0-F1) from thermophilic bacterium PS3 is co... more Purified dicyclohexylcarbodiimide-sensitive ATPase (TF0-F1) from thermophilic bacterium PS3 is composed of a water soluble part with ATP hydrolytic activity (TF1) and a water insoluble moiety (TF0). All of the five subunits (alpha, beta, gamma, delta, and epsilon) of TF1 were isolated. TF1 was reconstituted from the five subunits, which catalyzed an ATP-32Pi exchange and an ATP-driven enhancement of fluorescence of 1-anilinonaphthalene-8-sulfonate, when adsorbed on proteoliposome inlaid with TF0 (TF3-vesicles). Subunit epsilon and/or delta became firmly bound to TF0-vesicles and there was no preferential sequence in the binding. Both subunits were required for binding of the remaining subunits of TF1 to TF0-vesicles, but they did not modify the high H+ -permeability of TF0-vesicles. The addition of gamma but they did not modify the high H+-permeability of TFO-vesicles. The addition of gamma subunit together with epsilon and delta subunits caused a marked decrease of H+ -permeability of TF0-vesicles, similar to that induced by TF1. We conclude tentatively that the epsilon and delta subunits connect TF0 and the other subunits forming a part of a proton pathway, gamma is a gate of proton flow coupled to ATP hydrolysis (or synthesis), and alpha and beta subunits contain the active site for energy transformation. A possible model of subunit structure of TF1 is proposed.

Proceedings of the National Academy of Sciences, 1978

The H+-translocating ATPase complex from the thermophilic bacterium PS3 (TF0-F1) is composed of a... more The H+-translocating ATPase complex from the thermophilic bacterium PS3 (TF0-F1) is composed of a water-soluble part with ATP-hydrolyzing activity (TF1) and a membrane moiety with H+-conducting activity (TF0). TF0 was obtained by treating TF0-F1 with urea and removing contaminations on a carboxymethyl-cellulose column. This TF0 contained only two kinds of subunits, band 6 protein (13,500 daltons) and band 8 protein (5400 daltons), and it was active in H+ conduction and TF1 binding when reconstituted into proteoliposomes (TF0 vesicles). The binding of TF1 to TF0 present in vesicles restored energy-transducing activities, such as ATP-32Pi exchange, dicyclohexylcarbodiimide-sensitive ATPase, and ATP-dependent enhancement of 8-anilinonaphthalene-1-sulfonate fluorescence. Treatments such as protease digestion and chemical modification with acetic anhydride, succinic anhydride, or diazobenzenesulfonic acid destroyed the TF1-binding activity, which was caused by band 6 protein. Band 8 protein was a proteolipid that reacted specifically with dicylcohexyl-carbodiimide and seemed to play a central role in H+ conduction through the membrane.

Nucleic Acids Research, 1988

... SAT GTC TTA SAG TTT SAC GAT GGC ACC CCA GCT ACC ATG TCC CAG ATA SCC AAG GAT GTG A I A M A P P... more ... SAT GTC TTA SAG TTT SAC GAT GGC ACC CCA GCT ACC ATG TCC CAG ATA SCC AAG GAT GTG A I A M A P P I Y T D V L E F D D G T P A T H S Q I A K D V TGC ACC TTC CTG CGC TS6 GCA TCT SAS CCA GAG CAC SAC CAT CGA AAA CGC ATS SGG CTC AAS ATG ...

Nature Genetics, 1993

Machado-Joseph disease (MJD) is an autosomal dominant, multisystem neurodegenerative disorder inv... more Machado-Joseph disease (MJD) is an autosomal dominant, multisystem neurodegenerative disorder involving predominantly cerebellar, pyramidal, extrapyramidal, motor neuron and oculomotor systems. Although it was first reported in families of Portuguese-Azorean descent, MJD has also been described in non-Azorean families from various countries, being one of the most common hereditary spinocerebellar degenerations. With the use of highly polymorphic microsatellite DNA polymorphisms, we have assigned the gene for MJD to the long arm of chromosome 14 (14q24.3-q32) by genetic linkage to microsatellite loci D14S55 and D14S48 (multipoint lod score Zmax = 9.719).

Muscle & Nerve, 1994

We used Southern blot analysis and the polymerase chain reaction to analyze the tissue distributi... more We used Southern blot analysis and the polymerase chain reaction to analyze the tissue distribution of multiple mitochondrial DNA (mtDNA) deletions in a 45-year-old man with familial mitochondria1 myopathy. Southern blots showed two major types of abnormal mtDNA with approximately 4-and 8-kilobase deletions in the skeletal and extraocular muscles. The amount of muscle mtDNA with deletions correlated approximately with the severity of muscle involvement. The polymerase chain reaction showed multiple mtDNA deletions even in clinically asymptomatic tissues, the pattern of which differed with the type of tissue. Nucleotide sequences of several mtDNAs with deletions showed that the deletions were flanked by direct repeats consisting of 3 to 12 nucleotides. Leukocytes from the patient's affected sister and his mother exhibited the same mtDNA deletion pattern. Most of the same deletions were present in leukocytes obtained from the patient's father. 0 1994 John Wiley & Sons, Inc.

Journal of the Neurological Sciences, 1993

A point mutation of mitochondrial tRNALeu(UUR) gene is responsible for a MELAS (mitochondrial myo... more A point mutation of mitochondrial tRNALeu(UUR) gene is responsible for a MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) subgroup of mitochondrial encephalomyopathies. In most cases, the mutant mitochondrial DNA (mtDNA) coexists with normal mtDNA in a heteroplasmic manner. In order to quantify the content of mutant mtDNA, we developed a quantitative method of PCR. Using this method, the distribution of the mutant mtDNA was examined in 32 different tissues among 18 autopsied organs from a patient with MELAS, who had shown hypophyseal dysfunction. The percentage of the mutant mtDNA at nucleotide number 3243 in each tissue was ranged between 22% and 95%. The content of the mutant mtDNA was at the highest (95%) in the hypophysis and higher in the cerebral cortex than in the white matter. This study shows a possible correlation of tissue dysfunction with accumulation of the mutant mtDNA within the brain.

The Journal of Membrane Biology, 1976

Measurements were made of the difference in the electrochemical potential of protons (A fi H +) a... more Measurements were made of the difference in the electrochemical potential of protons (A fi H +) across the membrane of vesicles reconstituted from the ATPase complex (TFo 9 F1) purified from a thermophilic bacterium and P-lipids. Two fluorescent dyes, anilinonaphthalene sulfonate (ANS) and 9-aminoacridine (9AA) were used as probes for measuring the membrane potential (A ~u) and pH difference across the membrane (A pH), respectively.

Journal of Inherited Metabolic Disease, 1992