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K Kijima

Publications and source records attributed to K Kijima.

At least 37 records · Page 2Linked to original sources
PubMed1996

Translational regulation of angiotensin II type 1A receptor. Role of upstream AUG triplets.

The cDNA sequence of rat angiotensin II type 1A receptor (AT1AR) shows that AT1AR transcripts have AUG triplets in the 5'-leader region that may begin a short open reading frame encoding an 11-amino acid peptide. In this study, the mutational inactivation of the start codon of the short open reading frame in AT1AR-chloramphenicol acetyltransferase (CAT) reporter gene constructs resulted in a 2.6-fold increase in CAT activity, whereas CAT transcript levels were not affected. Furthermore, experiments with rat AT1AR cDNA-transfected Cos-7 cells revealed that mutagenesis of the upstream AUG increased the AT1AR protein up to 2.5-fold, although AT1AR transcript levels showed no changes. The synthetic peptide corresponding to the sequence of the short open reading frame significantly suppressed the amount of AT1AR product in the in vitro translation system. The inhibiting effect of the short open reading frame appears to operate at least in part at the level of translation initiation, because polysome analysis with transfected Cos-7 cells showed that mutagenesis of the upstream AUG resulted in a shift of AT1AR mRNA distribution from a smaller to larger fraction of polysomes. Taken together, these results show that the upstream AUG inhibits translational regulation, suggesting that the short open reading frame in the 5'-leader region of AT1AR transcripts has a certain role in the translation of AT1AR protein.

Animals↗
PubMed1996

Mechanical stretch induces enhanced expression of angiotensin II receptor subtypes in neonatal rat cardiac myocytes.

Mechanical stress plays a pivotal role in the development of cardiac hypertrophy during hemodynamic overload, and angiotensin (Ang) II secreted from stretched myocytes plays an important role in mechanical stretch-induced hypertrophy. In the present study, we examined stretch-induced expression of Ang II receptors in an in vitro stretch model using 1-day-old rat myocytes. Both Ang II type 1 receptor (AT1-R) and type 2 receptor (AT2-R) mRNA levels were upregulated by myocyte stretching with similar time courses: significant increases were evident 6 hours after stretching, maximal levels (2.8- and 3.3-fold, respectively) were observed at 12 hours, and these were sustained for up to 18 hours. Ang II receptor expression in fibroblast-rich cultures was not affected by stretching. Conditioned medium in which myocytes were stretched for 12 hours significantly downregulated AT1-R and AT2-R mRNA levels in recipient myocytes, and this effect was almost completely blocked by AT1-R antagonists but not AT2-R antagonists. Stretch-induced expression of AT1-R and AT2-R mRNAs was further increased by 27% and 31%, respectively, after pretreatment with AT1-R antagonists, suggesting that Ang II secreted from stretched myocytes downregulates both AT1-R and AT2-R. Western blot and binding assays showed that the number of AT1-Rs and AT2-Rs increased by 2.4- and 2.6-fold, respectively, without affecting receptor affinities. Inositol phosphate response to 0.5 mumol/L Ang II was enhanced 2.1-fold in stretched myocytes. Nuclear runoff assays and treatment with actinomycin D revealed that stretch-induced upregulation of AT1-R was mainly due to increased transcription, whereas that of AT2-R resulted from a stabilizing effect on AT2-R mRNA metabolism. Stretch-induced changes in levels of Ang II receptors were inhibited by genistein but not by H-7, staurosporin, and protein kinase C depletion or by BAPTA-AM. Exposure to cycloheximide did not affect stretch-induced changes. These findings indicate that nonsecretory pathways activated by myocyte stretching upregulate the expression of Ang II receptor subtypes transcriptionally and posttranscriptionally through mechanisms involving stretch-activated tyrosine kinases independently of de novo protein synthesis and that the AT1-R-mediated action of Ang II is functionally enhanced in stretched cardiac myocytes.

Angiotensin II↗
PubMed1996

Down-regulation by cAMP of angiotensin II type 2 receptor gene expression in PC12 cells.

The rat angiotensin II type 2 receptor (AT2-R) gene was isolated, and cis-regulatory regions in its 5'-flanking area were analyzed. Primer extension and RNase protection analyses revealed a single transcriptional initiation site at the position 24 bp downstream of the TATA box. The 5'-flanking region of AT2-R contained several cis-regulatory elements, such as AP-1, AP-2, C/EBP, NF-1, NF-IL6, NF-kappa B, and glucocorticoid- and cAMP-responsive elements (CRE). The treatment of PC12 cells with dibutyryl cAMP caused a marked decrease (90%) in the AT2-R mRNA level, which was blocked by the inhibitor of protein kinase A and did not require new protein synthesis. The protein level was also reduced 84% after a 24-h exposure to cAMP and the binding affinity was unchanged. The half-life of the AT2-R mRNA decreased -66% by cAMP as compared with control (18.4 +/- 0.4 h). Deletion and mutation analyses of the 5'-flanking region (1.2 Kb) revealed that there were one negative (-1,199 to -739) and two positive cis-regulatory regions (-739 to -436 and -59 to +45), and that the CRE motif located at -426 repressed (-23%) the promoter activity of the rat AT2-R gene. The region between -59 and +45 containing TATA box and AP-2 site accounted for 70% of the promoter activity. These findings indicate that the promoter activity of the rat AT2-R gene is modulated by several cis-regulatory regions and that cAMP markedly downregulates the expression of the AT2-R mainly by inducing AT2-R mRNA destabilization rather than CRE-mediated inhibition of the gene transcription. Thus, humoral factors that transduce cAMP as an intracellular signal may modulate AT2-R-mediated function of Ang II by reducing AT2-R expression.

Animals↗
PubMed1995

Gene transcription of angiotensin II type 2 receptor is repressed by growth factors and glucocorticoids in PC12 cells.

The rat angiotensin II type 2 receptor (AT2-R) expression was markedly downregulated by the mitogenic action of serum, growth factors and dexamethasone. The regulation by serum or growth factors did not affect the AT2-R mRNA half-life (18 h), whereas the AT2-R half-lives of dexamethasone-treated cells and proliferating cells decreased to 10 h and 15 h, respectively. Nuclear run-off assays indicated the mechanism of repression of AT2-R expression by serum, growth factors and dexamethasone or in proliferating cells to be, in large part, transcriptional. These findings indicate that transcription of the AT2-R gene is regulated in a growth state-dependent manner and suggest that this regulation provides a means by which cells can modulate their responsiveness to the actions of angiotensin II mediated through AT2-R.

Angiotensin II↗
PubMed1995

Identification of a negative cis-regulatory element and trans-acting protein that inhibit transcription of the angiotensin II type 1a receptor gene.

The rat angiotensin II type 1a receptor (AT1a-R) gene is expressed in a cell-specific manner. We demonstrated that the negative regulatory element (NRE) between -489 and -331 is active in PC12 cells (Murasawa, S., Matsubara, H., Urakami, M., and Inada, M. (1993) J. Biol. Chem. 268, 26996-27003). Gel retardation assays confirmed that PC12 cells have a trans-acting factor bound to the NRE. By means of a DNase I footprint assay we identified the core of the NRE as an (A+T)-rich sequence (TAATCTTTTATTTTA) located at nucleotides -456 to -442. Oligonucleotides corresponding to the NRE core sequence bound to nuclear protein. Site-directed mutagenesis at nucleotides -451 to -448 eliminated the specific protein/DNA binding and restored expression of the AT1a-R in transient transfection assays (2.7-fold increase). The NRE did not negatively affect the thymidine kinase promoter. No homology was found with known NREs, suggesting that this is a novel NRE. Southwestern blotting revealed a 53-kDa, specific binding protein in PC12 cells and the rat brain, but not in the liver, spleen, adrenal gland, and kidney. These findings demonstrate that the NRE of the rat AT1a-R is an (A+T)-rich sequence located at nucleotides -456 to -442 and the 53-kDa protein is a specific binding protein, and suggest that this protein may be a trans-acting factor which determines the neuron-specific down-regulation of the AT1a-R gene.

Angiotensin II↗
PubMed1995

Structure of the rat V1a vasopressin receptor gene and characterization of its promoter region and complete cDNA sequence of the 3'-end.

The gene encoding the rat V1a arginine vasopressin (AVP) receptor was isolated, and its structural organization and 5'-flanking region were characterized. In addition, the complete cDNA sequence of the major transcript of the rat V1a receptor gene was determined. Southern blots demonstrated a single copy of the V1a receptor gene in the rat genome, spanning a region of 3.8 kilobases (kb) and consisting of two exons and one intron (1.8 kb). The location of the intron was unique among G protein-coupled receptor genes in that the first exon encodes six of the seven transmembrane regions, the seventh region being encoded by the second exon. Primer extension, RNase protection, and rapid amplification of the 5'-end of the cDNA identified three transcriptional initiation sites (-405, -243, and -237), the major transcription initiation sites being mapped to positions -243 and -237 base pairs (bp) upstream of the ATG initiation codon (+1 bp). This portion of the 5'-flanking region has neither a TATA nor a CCAAT box, is GC-rich but has no GC box motif, and has features of promoters seen in housekeeping genes. Chimeras containing 2.2 kb of the 5'-flanking region and deletion analyses using the chloramphenicol acetyltransferase gene indicated that a "minimal" region, exhibiting promoter activity and tissue specificity, is located between nucleotides -296 and -221, when transfected into vascular smooth muscle cells. Gel mobility shift assay and Southwestern blotting suggested that approximately 30- and approximately 28-kDa nuclear proteins specifically bind to this region. Rapid amplification of the 3'-end of the cDNA showed that the major transcript terminates 442 bp downstream of the stop codon, in agreement with the mRNA size (2.1 kb). This study demonstrated a distinctive feature in the structural organization of the AVP-oxytocin receptor family genes, and characterization of the 5'-flanking region reported here will lead to a better understanding of the mechanism of transcriptional regulation of the rat V1a AVP receptor gene.

3T3 Cells↗
PubMed1995

Characterization of glucocorticoid response element of rat angiotensin II type 1A receptor gene.

The responsiveness of the rat angiotensin II type 1a and type 1b receptor (AT1a-R and AT1b-R) genes to glucocorticoid was examined in rat vascular smooth muscle cells (VSMCs) and the glucocorticoid response element (GRE) of the AT1a-R gene was characterized. Glucocorticoid induced an increase in AT1a-R mRNA levels, whereas AT1b-R mRNA levels were unaffected. The nuclear run-off assay indicated that the transcription of the AT1a-R gene, but not that of the AT1b-R gene, was increased by glucocorticoid. The mRNA stability of AT1a-R was unchanged by glucocorticoid. Promoter/chrolamphenicol acetyltransferase reporter analysis demonstrated that the 5'-flanking region of the AT1a-R gene was functional in rat VSMCs and established that the GRE motif between -770 to -756 could confer glucocorticoid responsiveness on the AT1a-R gene.

Angiotensin II↗
PubMed1995

Reversible left ventricular dysfunction associated with Guillain-Barré syndrome--an expression of catecholamine cardiotoxicity?

The patient was a 76-year-old female who had a history of Guillain-Barré syndrome 3 years previously; ST-segment elevation was noted in association with reversible left ventricular dysfunction. Left ventrioculogram and coronary angiograms were normal and ergonovine test was negative during the chronic period of Guillain-Barré syndrome. She was hospitalized again due to the recurrence of Guillain-Barré syndrome. Two days later, ST-segment elevation in leads V2 through V5 prompted us to perform cardiac catheterization, although she did not complain of any chest symptoms. A large akinetic area was found mainly around the apex on left ventriculography, despite the lack of coronary stenoses. Peak creatine kinase and C-reactive protein were 400 IU/ml and 3.5 mg/dl, respectively. Left ventricular dysfunction was normalized within one week. During the acute phase of the cardiac episode, plasma norepinephrine and epinephrine were 1340 pg/ml and 112 pg/ml, respectively. I123 metaiodobenzyl-guanidine myocardial scintigram 3 weeks after the episode showed an extensive apical defect which was improved markedly 3 months later. We think that this reversible left ventricular dysfunction was due to the synergistic toxic effect of mildly increased catecholamine and transiently damaged sympathetic nerve endings in the myocardium, presumably due to Guillain-Barré syndrome.

3-Iodobenzylguanidine↗
PubMed1994

Purification and properties of Saccharomyces cerevisiae cystathionine beta-synthase.

Cystathionine beta-synthase (beta-CTSase), which catalyses cystathionine synthesis from serine and homocysteine, was purified to homogeneity from Saccharomyces cerevisiae. The molecular mass of the enzyme was estimated to be 235 kDa by gel filtration and 55 kDa by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, indicating that it is a homotetramer. The N-terminal amino acid sequence of the enzyme perfectly coincided with that deduced from the nucleotide sequence of CYS4, except for the absence of initiation The purified beta-CTSase catalysed cysteine synthesis from serine (or O-acetylserine) and H2S. From this finding, we discuss the multifunctional nature and evolutionary divergence of S-metabolizing enzymes.

Amino Acid Sequence↗
PubMed1994

Large left-to-right shunt through a small atrial septal defect produced by progressive aortic stenosis in the elderly--a case report.

We present a 74-year-old female who showed a large left-to-right shunt through a small atrial septal defect presumably due to diastolic dysfunction of the left ventricle caused by the progression of aortic stenosis. Accordingly, elderly patients with even small atrial septal defect should be followed carefully, since diastolic dysfunction of the acquired left ventricular disorder could increase the left-to-right shunt.

Aged↗
PubMed1994

Markedly enlarged right atrium associated with physical signs of tricuspid regurgitation--a cause of congestive heart failure in the elderly.

We retrospectively examined 8 patients who had classical physical signs of tricuspid regurgitation associated with congestive heart failure, the cause of which was not identified by echocardiography. Exclusion criteria were as follows; 1) peak velocity of tricuspid regurgitation greater than 3 m/sec, 2) disturbance of left ventricular wall motion, 3) severe mitral regurgitation and/or aortic regurgitation by color Doppler echocardiography, and 4) structural abnormalities of tricuspid and mitral valve complexes. The subjects had a mean age of 81 years and all showed atrial fibrillation without tachycardia. Radiocardiography showed no significant left-to-right shunt. Two-dimensional echocardiography showed a markedly enlarged right atrium and slight enlargement of the right ventricle in all patients. A signal of tricuspid regurgitation was seen throughout the markedly enlarged right atrium on color Doppler echocardiography. Although neither hypoxemia nor hypercapnea were found in any of the patients, pulmonary function tests done in 6 patients were all abnormal. In chest x-ray films, 6 of the patients showed evidence of marked protrusion of the right heart border progressing over the course of several years. Right atrial enlargement due to both long-standing atrial fibrillation and presumably, to right ventricular diastolic dysfunction caused by aging made the tricuspid valve annuls annulus dilate to produce tricuspid regurgitation. In addition, concomitant mild lung disease produced a vicious cycle which led to more severe tricuspid regurgitation resulting in severe congestive heart failure. This pathophysiology can be a cause of congestive heart failure in the elderly.

Aged↗
PubMed1993

Tuberculous pericarditis: importance of adenosine deaminase activity in pericardial fluid.

We present a case of tuberculous pericarditis that was diagnosed early by a high titer of adenosine deaminase activity in the pericardial fluid and by a strongly positive tuberculin test. Within 2 weeks of initiation of treatment, pericardial effusion gradually decreased while clinical symptoms improved markedly. Culture from sputum, gastric juice, urine, and pericardial fluid were negative for tubercle bacillus. Measurement of adenosine deaminase activity in the pericardial fluid is a supplementary diagnostic test which is as important as for tuberculous pericarditis as it is for tuberculous pleuritis, because negative Ziehl Neelsen staining and culture for tubercle bacillus are common in tuberculous pericarditis.

Adenosine Deaminase↗
PubMed1993

[Formation of 8-hydroxydeoxyguanosine from 2'-deoxyguanosine and its decomposition by active oxygen].

8-hydroxydeoxyguanosine (8-OHdG) was formed from dG and isolated DNA by photosensitization with rose bengal (RB) and methylene blue (MB). 8-OHdG formed from dG was decomposed by the photosensitization with these dyes. Singlet oxygen was concerned with the formation and decomposition of 8-OHdG by photosensitization. Fe++ oxidized dG to 8-OHdG, which was decomposed by the addition of H2O2. 8-OHdG was formed and decomposed by the treatment of dG with Fe++, EDTA and ascorbic acid. Hydroxy radical (.OH) participated in the formation and decomposition of 8-OHdG by Fe++.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1993

[Hemolysis of isolated erythrocytes by UVA-sensitization of flavins].

Riboflavin (RF), flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) caused hemolysis of isolated rabbit erythrocytes by UVA-sensitization. Hemolysis induced by UVA-sensitization with RF and FMN was inhibited by 1.0 mM histidine and EDTA, and was promoted by 0.15 mM histidine and 0.01 mM NaN3. Hemolysis induced by irradiation in anaerobic condition was smaller than those in aerobic condition. Hemolysis was proceeded in the dark for 5 hours after the UVA-irradiation with RF and FAD. Erythrocyte treated by UVA-sensitization with RF easily caused hypotonic hemolysis.

Animals↗
PubMed1992

[Anesthetic management of a patient with norepinephrine-secreting neuroblastoma by using prostaglandin E1].

The anesthetic management of a 5-month-old male with norepinephrine-secreting neuroblastoma was described. Partial excision of the tumor was carried out under general anesthesia induced with enflurane, fentanyl and succinylcholine, and maintained with enflurane, nitrous oxide and oxygen. In this case, hypertension was observed intraoperatively and prostaglandin E1 was continuously infused at a rate of 0.1-0.5 micrograms.kg-1.min-1 to control blood pressure. Severe hypotension after removal of the tumor was not observed. Continuous administration of prostaglandin E1 was useful in this patient with norepinephrine-secreting neuroblastoma.

Alprostadil↗
PubMed1989

[Determination of seven ultraviolet absorbent in cosmetics by high speed liquid chromatography].

A rapid method for the HPLC determination of ultraviolet absorbent (UV abs.) in cosmetics was investigated. This method is based on the technique of solvent extraction of the sample by HPLC with silica-ODS (Develosil ODS-5) as the stationary phase A, B, C, and D as the eluent and the ultraviolet spectrophometer (310, 284 nm) as the detector. The plots of the peak height vs amount of seven UV abs. were linear between 0-20 micrograms/ml. The recoveries of UV abs. to a model sample at the level of 0.1% were 93.2-100.0% by this method. This method is simple and rapid, therefor it is applicable for the determination of UV abs. in cosmetics in routine analysis.

Absorption↗