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Shigeo Ohta

Publications and source records attributed to Shigeo Ohta.

47 records · Page 3Linked to original sources
PubMed2002

Protection against ischemic brain injury by protein therapeutics.

Preventing massive cell death is an important therapeutic strategy for various injuries and disorders. Protein therapeutics have the advantage of delivering proteins in a short period. We have engineered the antiapoptotic bcl-x gene to generate the super antiapoptotic factor, FNK, with a more powerful cytoprotective activity. In this study, we fused the protein transduction domain (PTD) of the HIVTat protein to FNK and used the construct in an animal model of ischemic brain injury. When added into culture media of human neuroblastoma cells and rat neocortical neurons, PTD-FNK rapidly transduced into cells and localized to mitochondria within 1 h. It protected the neuroblastomas and neurons against staurosporine-induced apoptosis and glutamate-induced excitotoxicity, respectively. The cytoprotective activity of PTD-FNK was found at concentrations as low as 0.3 pM. Additionally, PTD-FNK affected the cytosolic movement of calcium ions, which may relate to its neuroprotective action. Immunohistochemical analysis revealed that myc-tagged PTD-FNK (PTD-myc-FNK) injected i.p. into mice can have access into brain neurons. When injected i.p. into gerbils, PTD-FNK prevented delayed neuronal death in the hippocampus caused by transient global ischemia. These results suggest that PTD-FNK has a potential for clinical utility as a protein therapeutic strategy to prevent cell death in the brain.

Animals↗
PubMed2002

Association of polymorphisms of the estrogen receptor alpha gene with bone mineral density of the femoral neck in elderly Japanese women.

The estrogen receptor alpha gene is a candidate locus for genetic influence on bone mass. The possible association between two polymorphisms in the first intron of this gene, alone or in combination, and bone mineral density at various sites was examined in participants in the National Institute for Longevity Sciences Longitudinal Study of Aging, a population-based prospective cohort study of aging and age-related diseases. The relationship of the TC ( PvuII) and AG ( XbaI) polymorphisms in the first intron of the estrogen receptor alpha gene to bone mineral density was determined in 2230 subjects (1120 men, 1110 women) and in 2238 subjects (1128 men, 1110 women), respectively, all of whom were community-dwelling individuals aged 40-79 years. Bone mineral density at the radius was measured by peripheral quantitative computed tomography and that for the lumbar spine, right femoral neck, right trochanter, right Ward's triangle, and total body was measured by dual-energy X-ray absorptiometry. Estrogen receptor alpha genotypes were determined with an automated fluorescent allele-specific DNA primer assay system. Analysis of the TC ( PvuII) polymorphism revealed that bone mineral density for the total body, femoral neck, and trochanter was significantly lower in women aged 60 years or over with the CC genotype than in those with the TT genotype, but statistical significance was not achieved after adjustment for age, body mass index, and smoking status. Analysis of the AG ( XbaI) polymorphism revealed that bone mineral density for the femoral neck was significantly lower in women aged 60 years or over with the GG genotype than in those with the AA genotype. After adjustment for age, body mass index, and smoking status, bone mineral density for the femoral neck was significantly lower in women aged 60 years or over with the GG genotype than in those with the AA or AG genotypes. Analysis of combined genotypes in women aged 60 years or over revealed that bone mineral density for the femoral neck was significantly lower in women with the CC/ GG genotype than in those with the TT/ AA or TC/ AA genotypes. After adjustment for age, body mass index, and smoking status, bone mineral density for the femoral neck was significantly lower in women aged 60 years or over with the CC/ GG genotype than in those with other genotypes. No differences in bone mineral density at the various sites were detected among TC ( PvuII), AG ( XbaI), or combined genotypes in women aged under 60 years or in men. These results suggest that the estrogen receptor alpha gene is a susceptibility locus for bone mass, especially for the femoral neck, in elderly Japanese women.

Absorptiometry, Photon↗
PubMed2002

Wobble modification defect suppresses translational activity of tRNAs with MERRF and MELAS mutations.

By purifying mutant mitochondrial tRNAs, we were able to ascertain that post-transcriptional modification at the anticodon wobble uridine is absent in tRNA(Lys) with the 8344 MERRF mutation and in tRNA(Leu(UUR)) with either the 3243 or 3271 MELAS mutation. Both the MERRF and MELAS mutant tRNAs substantially lost their translational ability, the extent of the loss in each mutant corresponding to the reduction in actual mitochondrial translational activity. Lack of the wobble modification deprived mutant tRNA(Lys) of interaction with the cognate codons. These features indicate that the modification defect plays a primary role in the molecular pathophysiology of these mitochondrial diseases.

Journal Article↗
PubMed2002

Isolation and sequence analysis of the rat dihydrolipoamide succinyltransferase gene.

The dihydrolipoamide succinyltransferase (DLST) gene of the alpha-ketoglutarate dehydrogenase complex (alpha-KGDC) was isolated from a rat genomic DNA library and sequenced. This gene was composed of 15 exons and 14 introns like the human DLST gene. Sequence analysis of the promoter-regulatory region of the rat DLST gene-(Dlst) showed the possible presence of a CAAT box-sequence and of the sequences for an AP-2 site and three Sp1 sites, but no TATA box-sequence was evidenced. The nucleotide sequences of introns 1 and 4 of the rat Dlst were significantly homologous to those of introns 1 and 4 of the human DLST gene. The sequence analysis of the rat Dlst suggested that the exon coding for the E3- and/or E1-binding domain may have been lost from the gene during evolution in eukaryotic DLST, possibly after mitochondrial symbiosis because prokaryotic DLST possesses the E3- and/or E1-binding domain.

Acyltransferases↗
PubMedDate not supplied

Association of cholecystokinin-A receptor gene polymorphism with alcohol dependence in a Japanese population.

AIMS: Cholecystokinin (CCK), one of the most abundant neurotransmitter peptides, interacts with dopamine. Dopaminergic neurotransmission between the ventral tegmental area and the limbic forebrain is a critical neurobiological component of alcohol and drug self-administration. CCK modulates dopamine release in the nucleus accumbens via the CCK-A receptor (R). We recently determined the transcriptional start site of the human CCK-AR gene, and detected two sequence changes (-81A/G and -128G/T) in the promoter region. The aims of the present study were to determine the prevalence of the -81A/G and -128G/T polymorphism of the CCK-AR gene between alcoholics and normal control subjects and the occurrences of the polymorphisms in subtypes of alcoholics. METHODS: The above polymorphisms were examined in 435 alcoholics and 1490 control subjects. We excluded subjects with inactive ALDH2 and employed the subjects with ALDH2*1/2*1 (384 alcoholics and 792 controls). RESULTS: The allelic frequency of -81G in the CCK-AR gene polymorphism (-81A/G) was significantly higher in alcoholics than in control subjects. However, there were no differences between the two groups with respect to the frequency of -128G/T. Alcoholic patients with antisocial personality disorder and with first-degree alcoholic relatives were significantly associated with a higher frequency of the -81G allele. In addition, the age of onset of alcohol dependence was significantly earlier in patients with this allele. CONCLUSIONS: The CCK-AR gene -81A/G polymorphism, especially in the -81G allele, may be associated with intractable alcoholism.

Adult↗