Biomedical subjects

Y Hiroi

Publications and source records attributed to Y Hiroi.

54 records · Page 3Linked to original sources

PubMed1995

Salt-sensitive hypertension in transgenic mice overexpressing Na(+)-proton exchanger.

Essential hypertension is one of the most common diseases that exacerbate the risk of cardiovascular or cerebrovascular attacks. Although the etiology of essential hypertension remains unclear, recent investigations have revealed that an enhancement of Na(+)-proton (Na(+)-H+) exchange activity is a frequently observed ion transport abnormality in hypertensive patients and animal models. To test the hypothesis that increased Na(+)-H+ exchange causes hypertension, we produced transgenic mice overexpressing Na(+)-H+ exchanger and analyzed their Na+ metabolism and blood pressure. Urinary excretion of water and Na+ was significantly decreased in transgenic mice, and systolic blood pressure was elevated after salt loading. The impaired urinary excretion of Na+ suggested that the Na(+)-H+ exchanger overexpressed in the renal tubules increased reabsorption of Na+, which caused a blood pressure elevation by Na+ retention after excessive salt intake. Our results demonstrate that overexpression of Na(+)-H+ exchanger can be a genetic factor that interacts with excessive salt intake and causes salt-sensitive blood pressure elevation.

Animals↗

PubMed1995

Angiotensin II partly mediates mechanical stress-induced cardiac hypertrophy.

We have previously shown that mechanical stress induces activation of protein kinases and increases in specific gene expression and protein synthesis in cardiac myocytes, all of which are similar to those evoked by humoral factors such as growth factors and hormones. Many lines of evidence have suggested that angiotensin II (Ang II) plays a vital role in cardiac hypertrophy, and it has been reported that secretion of Ang II from cultured cardiac myocytes was induced by mechanical stretch. To examine the role of Ang II in mechanical stress-induced cardiac hypertrophy, we stretched neonatal rat cardiac myocytes in the absence or presence of the Ang II receptor antagonists saralasin (an antagonist of both type 1 and type 2 receptors), CV-11974 (a type 1 receptor-specific antagonist), and PD123319 (a type 2 receptor-specific antagonist). Stretching cardiac myocytes by 20% using deformable silicone dishes rapidly increased the activities of mitogen-activated protein (MAP) kinase kinase activators and MAP kinases. Both saralasin and CV-11974 partially inhibited the stretch-induced increases in the activities of both kinases, whereas PD123319 showed no inhibitory effects. Stretching cardiac myocytes increased amino acid incorporation, which was also inhibited by approximately 70% with the pretreatment by saralasin or CV-11974. When the culture medium conditioned by stretching cardiocytes was transferred to nonstretched cardiac myocytes, the increase in MAP kinase activity was observed, and this increase was completely suppressed by saralasin or CV-11974. These results suggest that Ang II plays an important role in mechanical stress-induced cardiac hypertrophy and that there are also other (possibly nonsecretory) factors to induce hypertrophic responses.

Angiotensin II↗

PubMed1995

Mechanical stress activates protein kinase cascade of phosphorylation in neonatal rat cardiac myocytes.

We have previously shown that stretching cardiac myocytes evokes activation of protein kinase C (PKC), mitogen-activated protein kinases (MAPKs), and 90-kD ribosomal S6 kinase (p90rsk). To clarify the signal transduction pathways from external mechanical stress to nuclear gene expression in stretch-induced cardiac hypertrophy, we have elucidated protein kinase cascade of phosphorylation by examining the time course of activation of MAP kinase kinase kinases (MAPKKKs), MAP kinase kinase (MAPKK), MAPKs, and p90rsk in neonatal rat cardiac myocytes. Mechanical stretch transiently increased the activity of MAPKKKs. An increase in MAPKKKs activity was first detected at 1 min and maximal activation was observed at 2 min after stretch. The activity of MAPKK was increased by stretch from 1-2 min, with a peak at 5 min after stretch. In addition, MAPKs and p90rsk were maximally activated at 8 min and at 10 approximately 30 min after stretch, respectively. Raf-1 kinase (Raf-1) and (MAPK/extracellular signal-regulated kinase) kinase kinase (MEKK), both of which have MAPKKK activity, were also activated by stretching cardiac myocytes for 2 min. The angiotensin II receptor antagonist partially suppressed activation of Raf-1 and MAPKs by stretch. The stretch-induced hypertrophic responses such as activation of Raf-1 and MAPKs and an increase in amino acid uptake was partially dependent on PKC, while a PKC inhibitor completely abolished MAPK activation by angiotensin II. These results suggest that mechanical stress activates the protein kinase cascade of phosphorylation in cardiac myocytes in the order of Raf-1 and MEKK, MAPKK, MAPKs and p90rsk, and that angiotensin II, which may be secreted from stretched myocytes, may be partly involved in stretch-induced hypertrophic responses by activating PKC.

Amino Acid Sequence↗

PubMed1995

[The relationship between blood sugar control and vascular complications in elderly diabetic patients--investigative study in 17 hospitals of Kochi Prefecture. Kochi Working Group on Diabetes Mellitus].

The aim of this study was to clarify whether the control state of fasting blood sugar can influence the occurrence of diabetic microangiopathy and macroangiopathy even in elderly patients with diabetes mellitus. In Kochi Prefecture 18 internal physicians participated in evaluating clinical courses of 898 patients, consisting of 466 males and 432 females, for an average of 69 months. Elderly cases aged 65 years or more old (group 1) consisted of patients who were aged 71.8 +/- 5.2 years old (M +/- SD). The average age of 481 adult cases under 65 years of age (group II) was 54.4 +/- 8.4 years old. Between the good and poor control groups, there was no difference in terms of blood pressure, body mass index (BMI) and serum lipids. Arteriosclerotic diseases such as myocardial infarction, cerebral infarction and arteriosclerosis obliterans appeared about as frequently in both the good and the poor control groups, while microangiopathies such as retinopathy, nephropathy and neuropathy were significantly more frequent in the poor control group compared to the good control group. The same tendency concerning these complications was seen in group II. Concerning treatment, diet treatment without drug treatment was significantly more frequent in the good control group compared to the poor control group, while hypoglycemic agents and subcutaneous insulin injection were used more often in the poor control group, the more severe state of diabetes mellitus in the latter group. Concerning the main reasons for good control, successful diet treatment was cited most often, followed by regular intake of medications. On the other hand disturbed diet treatment was the most frequent reason for poor control, indicating the strategic importance of diet treatment. Arteriosclerotic diseases were found more often in group I than group II, while the frequency of microangiopathies was similar. Concerning sexes, male patients tended to suffer more often from arteriosclerotic diseases than female patients, but the frequency of microangiopathy was similar. From the above findings it was concluded that poor control of fasting blood sugar level was related to microangiopathies in both non-elderly adult and elderly patients.

Aged↗

PubMed1995

Pyridoxal 5'-phosphate modulates expression of cytosolic aspartate aminotransferase gene by inactivation of glucocorticoid receptor.

The level of mRNA for cytosolic aspartate aminotransferase (cAST) in the liver of vitamin B6-deficient rats was found to be 7-fold higher than that of the control rats. The administration of hydrocortisone to adrenalectomized vitamin B6-deficient rats induced expression of hepatic cAST mRNA and the induction was suppressed by the simultaneous administration of pyridoxine. Since the 5' regulatory region of the rat cAST gene contains several sequences showing homology to glucocorticoid-responsive elements, we synthesized an oligonucleotide probe of glucocorticoid-responsive element sequence and assayed the binding activity of liver nuclear extract to the oligonucleotide by gel mobility shift analysis. We found that the binding activity of nuclear extract prepared from the liver of vitamin B6-deficient rats was far greater than that of the control rats, indicating that the DNA-binding activity of glucocorticoid receptor was enhanced by vitamin B6 deficiency. We further found that preincubation of the nuclear extract from the vitamin-deficient liver with pyridoxal 5'-phosphate brought about a rapid and extensive decrease in the binding of the extract to the glucocorticoid-responsive element. Congeners of pyridoxal phosphate, such as pyridoxamine 5'-phosphate, pyridoxal, pyridoxamine and pyridoxine, did not show an inhibitory effect. These observations suggest that pyridoxal 5'-phosphate modulates cAST gene expression by inactivating the binding activity of glucocorticoid receptor to glucocorticoid-responsive elements.

Adrenalectomy↗

PubMed1994

A lysosomal arylamidase is a member of a larger family of peptidases in lysosomes.

One form (form VI) of lysosomal arylamidase, having a molecular weight of 135,000 and an isoelectric point of 7.8, was purified from rat liver to apparent electrophoretic homogeneity. The enzyme consisted of three identical polypeptides with a molecular weight of 45,000, as judged by disk electrophoresis in the presence of sodium dodecyl sulfate (SDS). The enzyme hydrolyzed di- and tripeptides. The enzyme released a N-terminal amino acid from Leu5-enkephalin and Met-Lys-bradykinin; these have a tyrosine and a methionine at the N-terminus, respectively. The enzyme did not hydrolyze bradykinin, angiotensin and melanocyte-stimulating hormone release-inhibitory factor (MIF); these have a basic amino acid, an acidic amino acid, and a proline at the N-terminus, respectively.

Amino Acid Sequence↗

PubMed1993

Some properties of lysosomal arylamidase in rat liver.

Lysosomal arylamidase in rat liver was reassessed. The arylamidase was distinguishable into seven types having different isoelectric points by isoelectric fractionation. All the types hydrolyzed valine beta-naphthylamide most rapidly among amino acid beta-naphthylamides tested, but did not hydrolyze arginine beta-naphthylamide. These enzymes exhibited maximum activities at pH 7.0. They had a molecular weight of 135,000 by gel filtration on a Sephacryl S-200. They were all inhibited by sulfhydryl-blocking reagents and activated by sulfhydryl compounds, indicating to be cysteine proteases.

Aminopeptidases↗

PubMed1992

Ubiquitin metabolism in HeLa cells starved of amino acids.

Radio-iodinated ubiquitin (Ub) was introduced into HeLa cells by red blood cell-mediated microinjection. The half-life and solubility of Ub, as well as the molecular weight distributions of Ub conjugates, were then measured in HeLa cells grown in complete medium or in medium lacking amino acids and fetal calf serum. Ub metabolism was similar in the two sets of cells. Thus, the dramatic changes in Ub metabolism induced by thermal stress are not observed upon amino acid deprivation.

Adenosine Triphosphate↗

PubMed1992

Purification and properties of an aminopeptidase from rat-liver cytosol.

An aminopeptidase was purified from the rat-liver cytosolic fraction to apparent electrophoretic homogeneity. The enzyme is a monomeric protein of 95 kDa, having an isoelectric point of 4.9. Amino acid analyses indicate that the enzyme is rich in acidic amino acids and is poor in cysteine. The enzyme hydrolyzed a broad spectrum of amino acid beta-naphthylamides at a neutral pH. The enzyme also hydrolyzed di-, tri-, and oligopeptides, including physiologically active peptides such as enkephalins and Met-Lys-bradykinin. The enzyme was inhibited by metal-chelating agents, sulfhydryl-reactive reagents, N-P-tosyl-L-phenylalaninechloromethyl ketone, N-P-tosyl-L-lysinechloromethyl ketone, and puromycin but not by protease inhibitors of microbial origin. The enzyme was activated by the addition of Co2+ and sulfhydryl compounds. The aminopeptidase enhanced proteolysis when the enzyme was added to the protease assay system with purified rat-liver cytosolic neutral protease, suggesting the cooperative action of aminopeptidase in the overall process of protein degradation.

Amino Acid Sequence↗

PubMed1992

Lipophilic soluble protein represents labile protein in rat liver.

Lipophilic proteins, having higher turnover rates than the average of the total soluble protein pool, were separated from soluble rat-liver proteins on alkyl agarose column. The quantitative immunoprecipitation, using the antibody against the lipophilic proteins, showed that the soluble proteins from the liver of fed rats contained about twice as much lipophilic proteins as that of 3-day-starved rats. This result indicates that the lipophilic proteins, at least in part, represent labile protein in rat liver.

Animals↗

PubMed1987

Purification and characterization of a neutral protease from rat-liver cytosolic fraction.

Rat liver cytosol contains a neutral protease which degrades acetylated hemoglobin and some urea-denatured proteins maximally at pH 7.5. The enzyme was purified to homogeneity by conventional chromatographic techniques. It appears to be a metalloprotease since it is inhibited by EDTA and o-phenanthroline, the metal-depleted enzyme can be reactivated by Co2+, Zn2+, Mn2+, or Mg2+, and it is not inhibited by reagents specific for carboxyl, seryl, or thiol proteases. The enzyme has an apparent molecular weight of 200,000 as determined on Sephacryl S-200 column chromatography, and electrophoresis in sodium dodecyl sulfate showed 3 protein bands corresponding to the molecular weights of 110,000, 74,000, and 40,000.

Animals↗

PubMed1986

A case of Sjögren's syndrome with valvular diseases.

The case of a 61 year old woman with Sjögren's syndrome with aortic and mitral stenosis is reported. She suffered from rheumatic fever at a young age. Physical and echocardiographic examinations showed findings of mitral and aortic valve stenosis. In addition, she had experienced xerostomia, a gritty sensation in the eyes and Raynaud's phenomenon. Blood examination showed hypergammaglobulinemia, positive rheumatoid factor, antinuclear and anti-Ro (SS-A) antibodies. The diagnosis of Sjögren's syndrome was confirmed by sialography and biopsy of the labial salivary gland. The combination of valvular disease and Sjögren's syndrome is rare and the etiological correlation is discussed.

Antibodies, Antinuclear↗

PubMed1977

Synthesis of mono- and bifunctional alpha-methylene lactone systems as potential tumor inhibitors.

Synthetic nono- and bifunctional alpha-methylene lactone derivatives including deoxyvernolepin and kihydrodeoxyvernolepin were tested as inhibitors of the growth of CCRF-CEM human lymphoblastic leukemia cells in culture. The range of ID-50 values for compounds 1-7 (ca. 10(-5)-10(-6)M) was roughly comparable to the doses observed earlier in the CCRF-CEM cell system with synthetic alpha-methylene-gamma-butyrolactones. Of significance is that dihydrodeoxyvernolepin and deoxyvernolepin were at least an order of magnitude more active than natural vernolepin.

Animals↗

PubMed1976

The state of lysosomes and protein turnover in rat liver. Effect of excess vitamin A.

Administration of excess vitamin A to rats induces labilization of liver lysosomal membranes, as shown by the release of lysosomal cathepsins upon tissue homogenization. The effect of lysosomal labilization on liver protein turnover was investigated. The apparent turnover rate of liver proteins in the hypervitaminotic animals, as measured by a double isotope-labeling technique (Glass and Doyle (1972) J, Biol. Chem, 247, 5234-5242), was found to be the same as that in control animals. Neutral and alkaline fructose-1, 6-biphosphatase [EC 3.3.3.11] activities in the liver were also found to be unchanged in hypervitaminosis A. These data indicate that the rate of intracellular protein degradation is not determined by the level of "free cathepsins. Protein synthesis in the livers of the hypervitaminotic animals was partially imparied, as shown by the shift of polysomal profiles toward lighter aggregates.

Amino Acids↗

PubMed1973