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M Imagawa

Publications and source records attributed to M Imagawa.

At least 55 records · Page 3Linked to original sources
PubMed1998

CCAAT/enhancer-binding protein delta gene expression is mediated by autoregulation through downstream binding sites.

CCAAT/enhancer-binding protein delta (C/EBP delta) transcription factor is sharply induced at the early stage of the acute phase response. We previously reported that the C/EBP delta gene expression is induced by the acute-phase response factor/signal transducers and activators of transcription 3 (APRF/STAT3). However, the expression level of the C/EBP delta gene is relatively high up to several hours after the stimulation, whereas APRF/STAT3 is inactivated within one hour. In this report, we identified the two C/EBP delta binding sites at the downstream region of this gene. The binding analysis revealed that both of these sites bound recombinant C/EBP delta protein. A cotransfection analysis identified these sites as the cis-elements for the autoregulation. We conclude that the C/EBP delta gene is activated by APRF/STAT3, and the expression level is then maintained by an autoregulation mechanism.

Animals↗
PubMed1997

Identification of the transcriptional repression domain of nuclear factor 1-A.

We previously showed that nuclear factor 1-A (NF1-A) binds to the silencer elements in the glutathione transferase P (GST-P) gene, and the carboxy terminal region of NF1-A represses the transcription activity of human metallothionein IIA (hMTIIA) promoter. In this study, we identified a repression region which is divided into two 100 amino acid domains (RD1 and RD2). RD1 increased the repression activity of RD2 to the hMTIIA promoter activity. The NF1-A repression domain inhibited the promoter activities of not only the hMTIIA gene but also those of the GST-P and CCAAT/enhancer binding protein delta genes. RD1 and RD2 had abundant serine and glycine residues, and proline and serine residues, respectively. Whereas some repression domains identified previously are enriched with alanine, proline, or serine, and are associated with the general transcription factors, the NF1-A repression domains did not interact with transcription factor IIB, TATA-binding protein (TBP), or TBP-associated factors in vitro.

CCAAT-Enhancer-Binding Proteins↗
PubMed1997

T/G polymorphism at intron 9 of presenilin 1 gene is associated with, but not responsible for sporadic late-onset Alzheimer's disease in Japanese population.

To investigate whether presenilin 1 (PS1) gene, a major causative gene of familial early-onset Alzheimer's disease (AD), also contributes to the etiology of sporadic AD, we evaluated associations between Japanese AD and polymorphisms located at 14q24.3. While the D14S43 and FOS loci showed no association with either early- or late-onset AD, late-onset AD carrying no APOE-epsilon4 allele was associated with the G allele of the T/G polymorphism located at intron 9 of the PS1 gene (P = 0.016). Considering another study showing a positive association between AD and the T allele, this polymorphism is associated with, but not responsible for sporadic late-onset Alzheimer's disease.

Age of Onset↗
PubMed1997

alpha 1-Antichymotrypsin as a risk modifier for late-onset Alzheimer's disease in Japanese apolipoprotein E epsilon 4 allele carriers.

In the Japanese population, sporadic late-onset Alzheimer's disease (LOAD) cases had significantly higher frequencies of the A allele of alpha 1-antichymotrypsin (ACT) gene as well as the epsilon 4 allele of apolipoprotein E (APOE) gene than controls. The odds ratio for LOAD in APOE4 carriers with the ACT-A allele was more than six times that in APOE4 carriers without the ACT-A allele (21.1 vs 3.2). These results indicate that the ACT-A allele is a risk modifier for LOAD in APOE4 carriers.

Age of Onset↗
PubMed1997

Properties of saccular nerve-activated vestibulospinal neurons in cats.

Axonal pathways, projection levels, conduction velocities, and locations of the cell bodies of saccular nerve-activated vestibulospinal neurons were studied in decerebrated cats and anesthetized cats, using a collision test of orthodromic and antidromic spikes. The saccular nerve was selectively stimulated by bipolar tungsten electrodes. Three monopolar electrodes were inserted into the left and right lateral vestibulospinal tract (LVST) and medial vestibulospinal tract (MVST) of the C1 segment, to determine the pathway of axons. Three pairs of similar electrodes were positioned bilaterally in the C3-4, T1, and L3 segments to examine projection levels. Another monopolar electrode was placed in the oculomotor nucleus to determine whether saccular nerve-activated vestibulospinal neurons have branches ascending to the oculomotor nucleus. Of 145 vestibular neurons orthodromically activated by stimulation of the saccular nerve, 46 were activated from the C1 segment antidromically. Forty-three were second-order vestibulospinal neurons and 3 were third-order vestibulospinal neurons. Four saccular nerve-activated vestibulospinal neurons were also antidromically activated from the oculomotor nucleus. Sixty-three percent of the saccular nerve-activated vestibulospinal neurons descended through the MVST; one-third of these terminated in the upper cervical segments, one-third reached the lower cervical segments and the remaining one-third reached the upper thoracic segments. Thirty percent of the saccular nerve-activated vestibulospinal neurons descended through the ipsilateral LVST; most of these reached the upper thoracic segments. Seven percent of the saccular nerve-activated vestibulospinal neurons descended through the contralateral vestibulospinal tracts terminating in the upper cervical segments. Most of the saccular nerve-activated vestibulospinal neurons originated in the caudal part of the lateral nucleus and rostral part of the descending nucleus.

Animals↗
PubMed1997

Human transferrin (Tf): a single mutation at codon 570 determines Tf C1 or Tf C2 variant.

Transferrin (Tf) has many variants, as revealed by isoelectric focusing (IEF). Although these Tf variants have long been thought to arise from the multiple alleles at single Tf locus, amino acid substitution related to the two major variants, Tf C1 and Tf C2, has so far not been reported. We investigated the difference responsible for Tf C1 and Tf C2 variants and identified a single base change in exon 15 of the Tf gene resulting in the phenotypes on IEF. C/T base substitution at codon 570 replaced Pro in Tf C1 with Ser in Tf C2. Based on this nucleotide substitution, we established PCR-based genotyping for the Tf C1 and Tf 2 alleles.

Codon↗
PubMed1997

Association of transferrin C2 allele with late-onset Alzheimer's disease.

Transferrin (Tf), an iron-transporting protein, has many variants, but C1 and C2 variants account for the majority of the population in all races. Since Tf is reported to be immunocytochemically detectable in senile plaques in Alzheimer's disease (AD), we have examined the Tf allele frequency among AD patients. The C2 allele frequency in late-onset AD patients is significantly higher than that in age-matched controls. Unexpectedly, the C2 allele frequency in AD patients homozygous for the ApoE epsilon 4 allele is markedly increased, i.e., it is twice as high as that in the remaining AD patients carrying zero or one copy of the epsilon 4 allele.

Adult↗
PubMed1997

Identification of a novel vitamin D response element from the rat genome.

1 alpha,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], the active form of vitamin D3, has been thought to be a multifunctional agent. In order to discover novel roles of 1,25-(OH)2D3, we have been looking for new genes that are regulated by 1,25-(OH)2D3. Because the actions of 1,25-(OH)2D3 are mediated through the vitamin D receptor (VDR), that is a DNA binding transcription factor, vitamin D regulated genes should have VDR binding sites in their regulatory regions. In this paper, we describe a novel vitamin D response element (VDRE)-containing sequence, clone 3, which was isolated through binding to VDR. DNA sequence analysis of clone 3 did not reveal any significant similarity with sequences reported previously. Clone 3 had two regions consisting of a direct repeated sequence of AGTTCA motifs, both of which bound to VDR independently. Whereas each direct repeat sequence alone could not mediate transcriptional activation efficiently, with their co-existence there was a strong response to 1,25-(OH)2D3, indicating that these two direct repeated sequences act cooperatively.

Animals↗
PubMed1997

Nuclear factor 1 family proteins bind to the silencer element in the rat glutathione transferase P gene.

We have previously identified a silencer region in the glutathione transferase P (GST-P) gene, of which the expression is completely repressed in liver of the rat. At least three trans-acting factors bind to multiple cis-elements in this region. Since GST-P silencer 4 (GSP4) is a dominant element in this silencer, we purified the GSP4 binding protein, called Silencer Factor A (SF-A). Purified SF-A was separated into several proteins on an SDS-polyacrylamide gel, and the amino acid sequences of four major components of SF-A were determined. The amino acid sequences of three fragments were identical to those of rat NF1-L, and that of the other fragment was the same as that of hamster NF1/Red1. It is known that nuclear factor 1 (NF1) family proteins are encoded by at least four independent genes in vertebrates, and NF1-L and NF1/Red1 are derived from different genes, NFI-A and NFI-B, respectively. The microsequencing of SF-A revealed that at least two types of NF1 existed in rat liver. Functional analysis by using GAL4-fusion protein in HepG2 cells revealed that NFI-A represented the transcription activity from human metallothionein IIA promoter. Our findings indicate that multiple forms of the NF1 family bind to the silencer region and contribute to the negative regulation of the GST-P gene expression.

Amino Acid Sequence↗
PubMed1997

CCAAT/enhancer-binding protein delta gene expression is mediated by APRF/STAT3.

The CCAAT/enhancer-binding protein delta (C/EBP delta) transcription factor is known to be rarely expressed but sharply induced at an early stage of the acute phase response. To investigate the regulation mechanisms for this induction, the 5'-flanking region of the rat C/EBP delta gene was isolated. Functional analyses involving transfection and footprinting indicated that the upstream region up to - 175 bp is sufficient for the full basal activity in rat fibroblast 3Y1 cells. At least three cis-elements including a GC box are involved in this activity. When HepG2 cells were treated with interleukin-6 (IL-6), C/EBP delta mRNA was rapidly induced. Transfection and gel shift analyses identified the binding site for the acute phase response factor/signal transducers and activators of transcription (APRF/STAT3). These findings strongly indicate that C/EBP delta gene expression is mediated by APRF/STAT3, which is phosphorylated for the activation through the IL-6 receptor when cells are treated with IL-6, and trans-activates the other acute phase response genes.

Animals↗
PubMed1997

Genomic organization of the rat nuclear factor I-A gene.

The nuclear factor 1 (NF1) protein family functions as a cellular transcription factor as well as an adenovirus DNA replication factor. This family consists of four subtypes, NFI-A, NFI-B, NFI-C, and NFI-X, each encoded by a different gene. Each subtype possesses different isoforms generated by alternative splicing. To date, only a porcine NFI-C gene has been cloned, and the gene structures of the other NF1 proteins have not yet been identified. We recently isolated four kinds of NFI-A cDNA clones from the rat liver. To gain additional insight into the structure of NFI-A, we isolated the rat NFI-A gene. This gene is composed of 11 exons spanning over 70 kb. All of the exon/intron boundaries are consistent with the GT/AG rule, and consensus sequences surrounding the splice boundaries are also found. The 5'-flanking region lacks a canonical TATA box, but contains several GC-box and AP2 binding sites. A 5'-rapid amplification of cDNA end analysis indicated that the transcription of the NFI-A gene is initiated at multiple sites. We also found conservation in the genomic structure between the rat NFI-A and the porcine NFI-C, suggesting that duplication of an ancestral gene occurred rather recently to produce the NFI-A and NFI-C genes.

Animals↗
PubMed1997

Role of platelet-activating factor in two-kidney, one-clip hypertension.

BACKGROUND: Platelet-activating factor (PAF) is a bioactive phospholipid which is a potent hypotensive agent. To investigate the role of PAF in renovascular hypertension, we determined the PAF concentration and its production level assessed by the activity of cholinephosphotransferase (CPT) in renal tissue and examined the effect of a PAF antagonist on the mean arterial pressure (MAP) in control and two-kidney with one clipped (2K1C) hypertensive rats. MATERIALS AND METHODS: The concentration of PAF and CPT in the renal medulla and cortex were determined by radioassay. Also, the effect of a PAF antagonist, CV-6209, on MAP was also examined in both 2K1C hypertensive and normal control rats. RESULTS: The PAF concentration and CPT activity were significantly higher in the medulla than in the cortex in both 2K1C hypertensive and normal control rats, and both values in the medulla were also significantly higher in the clipped kidney than in the contralateral unclipped kidney or in control rat kidneys. We also observed a significant negative correlation between the PAF concentration in the medulla, and the medulla weight in the clipped kidney of 2K1C hypertensive rats. Infusion of the PAF antagonist, CV-6209, did not affect MAP in 2K1C hypertensive rats, but was significantly increased (P < 0.05) in control rats. CONCLUSIONS: These findings suggest that PAF, whose production is induced by renal ischemia due to renal artery stenosis, plays an important role in the renomedullary vasodepressor system, but the effect of PAF as a vasodilator in the peripheral vessels is limited in 2K1C hypertension.

Animals↗
PubMed1997

Sacculocollic reflex arcs in cats.

Neuronal connections and pathways underlying sacculocollic reflexes were studied by intracellular recordings from neck extensor and flexor motoneurons in decerebrate cat. Bipolar electrodes were placed within the left saccular nerve, whereas other branches of the vestibular nerve were removed in the inner ear. To prevent spread of stimulus current to other branches of the vestibular nerve, the saccular nerve and the electrodes were covered with warm semisolid paraffin-Vaseline mixture. Saccular nerve stimulation evoked disynaptic (1.8-3.0 ms) excitatory postsynaptic potentials (EPSPs) in ipsilateral neck extensor motoneurons and di- or trisynaptic (1.8-4.0 ms) EPSPs in contralateral neck extensor motoneurons, and di- and trisynaptic (1.7-3.6 ms) inhibitory postsynaptic potentials (IPSPs) in ipsilateral neck flexor motoneurons and trisynaptic (2.7-4.0 ms) IPSPs in contralateral neck flexor motoneurons. Ipsilateral inputs were about twice as strong as contralateral ones to both extensor and flexor motoneurons. To determine the pathways mediating this connectivity, the lateral part of the spinal cord containing the ipsilateral lateral vestibulospinal tract (i-LVST) or the central part of the spinal cord containing the medial vestibulospinal tracts (MVSTs) and possibly reticulospinal fibers (RSTs) were transected at the caudal end of the C1 segment. Subsequent renewed intracellular recordings following sacculus nerve stimulation indicated that the pathway from the saccular nerve to the ipsilateral neck extensor motoneurons projects though the i-LVST, whereas the pathways to the contralateral neck extensors and to the bilateral neck flexor motoneurons descend in the MVSTs/RSTs. Our data show that sacculo-neck reflex connections display a qualitatively bilaterally symmetrical innervation pattern with excitatory connections to both neck extensor motoneuron pools, and inhibitory connections to both neck flexor motoneuron pools. This bilateral organization contrasts with the unilateral innervation scheme of the utriculus system. These results suggest a different symmetry plane along which sacculus postural reflexes are organized, thus supplementing the reference planes of the utriculus system and allowing the gravistatic system to represent all three translational spatial degrees of freedom. We furthermore suggest that the sacculocollic reflex plays an important role in maintaining the relative position of the head and the body against the vertical linear acceleration of gravity.

Afferent Pathways↗
PubMed1997

The beta APP717 Alzheimer mutation increases the percentage of plasma amyloid-beta protein ending at A beta42(43).

We measured plasma levels of amyloid beta protein (A beta) ending at positions 40 (A beta40) and 42(43) [A beta42(43)] in six carriers of beta APP717 (Val to Ile) mutation linked to familial Alzheimer's disease (FAD) as well as in patients with sporadic AD (sAD) and controls. The percentage and the level of A beta42(43) were significantly higher in carriers of beta APP717 mutation relative to sAD, whereas A beta40 levels were decreased. In contrast, A beta levels and ratios were at similar levels in sAD, regardless of the stage of the disease, compared with non-AD neurologic disease controls and nondemented control individuals. These results suggest that the reported increase in the percentage of A beta42(43) secretion in transfected cells with beta APP717 mutant genes actually takes place in the bodies of carriers of beta APP717 mutation, and that plasma A beta could be used as an indicator of the alterations of beta APP/A beta metabolism in subtypes of AD.

Adult↗