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Y Oiso

Publications and source records attributed to Y Oiso.

At least 91 records · Page 5Linked to original sources
PubMed1996

Gene screening of thyroxine-binding globulin (TBG) deficiencies in the Japanese: only two mutations account for TBG deficiencies in the Japanese.

T4-binding globulin (TBG) is the principal transport protein for thyroid hormone in the circulation. Twelve mutations in the human TBG gene have been reported, and the inheritance of those variant TBGs was shown to be X-chromosome linked. We previously reported a nucleotide deletion at the codon 352 (TBG-CDJ) and a nucleotide substitution at the codon 362 (TBG-PDJ) of the TBG gene in a Japanese male manifesting TBG complete deficiency and partial TBG deficiency, respectively. In this communication we investigate the prevalence of both mutations among 50 unrelated Japanese subjects manifesting complete or partial TBG deficiency from various areas of the Japanese Archipelago. Mutant alleles were identified by amplification of their genomic DNAs by PCR with allele-specific primers. In addition, the presence of a polymorphic mutation in codon 283 (TBG-Poly) in these variants was investigated. All male subjects manifesting complete TBG deficiency (n = 30) and all female subjects manifesting partial TBG deficiency (n = 4) were demonstrated to be hemizygotes and heterozygotes for the mutation of TBG-CDJ, respectively. All male subjects manifesting partial TBG deficiency (n = 16) were shown to have the mutation of TBG-PDJ as hemizygotes. TBG-Poly was consistently absent from these variants. We conclude that only TBG-CDJ and TBG-PDJ may account for complete and partial TBG deficiencies in the Japanese.

Alleles↗
PubMed1996

Molecular analysis of females manifesting thyroxine-binding globulin (TBG) deficiency: selective X-chromosome inactivation responsible for the difference between phenotype and genotype in TBG-deficient females.

T4-binding globulin (TBG) is the major transport protein of thyroid hormone in man. Inherited TBG abnormalities were manifested fully in hemizygous males and partially in heterozygous females and transmitted in an X-chromosome-linked fashion, compatible with its location on Xq21-22. We have previously reported that complete deficiency (CD) and partial deficiency (PD) in Japanese subjects resulted from two distinct mutations of the TBG gene, TBG-CDJ and TBG-PDJ, respectively. Recently, we encountered a female manifesting TBG-CD and herein investigated the molecular mechanisms. She was found to possess TBG-CDJ and common-type TBG (TBG-C) alleles by characterizing the TBG gene. Then, X-chromosome inactivation status was evaluated in her family members using a phosphoglycerate kinase (PGK) gene, located on Xq13. Three TBG-CDJ heterozygotes and one unaffected female, confirmed to be PGK heterozygotes for a polymorphic BstXI site, were analyzed. Only the CD female was shown to undergo selective inactivation by examining the BstXI site in amplified products after digestion with a methylation-sensitive enzyme, HpaII. Among an additional eight informative females with TBG deficiency, one heterozygous female for TBG-PDJ shared this selective inactivation pattern. Moreover, the X-chromosome with TBG-C was suggested to be inactivated selectively from the linkage of PGK and TBG alleles recognized in eight of nine family members. Selective X-chromosome inactivation was considered to be the cause of a female heterozygous for TBG-CDJ or -PDJ manifesting the same phenotype as a hemizygote.

Base Sequence↗
PubMed1995

The expression of pituitary adenylate cyclase-activating polypeptide (PACAP) mRNA in rat brain: possible role of endogenous PACAP in vasopressin release.

We investigated the expression of pituitary adenylate cyclase-activating polypeptide (PACAP) mRNA in rat brain by in situ hybridization. PACAP mRNA was prominently expressed in arcuate nucleus (ARC). Three days of water deprivation significantly increased plasma arginine vasopressin and markedly potentiated the expression of PACAP mRNA in ARC. These results suggest that PACAP in ARC may play some physiological role, possibly one of which may be the control of vasopressin release.

Animals↗
PubMed1995

Effect of prostaglandin E2 on phospholipase D activity in osteoblast-like MC3T3-E1 cells.

Recent evidence indicates that phosphatidylcholine breakdown by phospholipase D (PLD) is an important cellular control mechanism. We investigated the signaling pathway participating in prostaglandin E2 (PGE2)-induced PLD activation in osteoblast-like MC3T3-E1 cells. PGE2 stimulated PLD activity, as measured by choline generated from phosphatidylcholine, just after the stimulation. The reaction reached a plateau 15 minutes later. PGE2 stimulated PLD activity in a dose-related manner and also increased inositol phosphate (IP) formation. However, the EC50 value for PGE2-induced IP formation is lower than that for PLD activation. 12-O-Tetradecanoylphorbol-13-acetate (TPA), a protein kinase C (PKC) activator, stimulated PLD activity, and a combination of PGE2 and TPA potentiated it in an additive manner. Although NaF, a heterotrimeric GTP-binding protein activator, significantly stimulated PLD activity, this effect was not augmented by combination with PGE2. PGE2-induced PLD activity was markedly suppressed by either chelating extracellular Ca2+ by EGTA or pertussis toxin. These findings suggest that osteoblasts might have at least two PLD activation mechanisms which involve PKC-dependent or -independent pathways. However, present results indicate that PKC is unlikely to be essential to PGE2-induced PLD activation. On the contrary, pertussis toxin-sensitive GTP-binding protein and extracellular Ca2+ might play important roles in the pathway of PGE2-induced PLD activation.

3T3 Cells↗
PubMed1995

Tyrosine kinase regulates phospholipase D activation at a point downstream from protein kinase C in osteoblast-like cells.

It has recently been shown that the activation of protein kinase C (PKC) induces protein tyrosine phosphorylation in osteoblast-like MC3T3-E1 cells. We previously reported that the activation of PKC stimulates phosphatidylcholine-hydrolyzing phospholipase D in these cells. In this study, we examined whether protein tyrosine kinase is involved in the PKC-induced activation of phospholipase D in MC3T3-E1 cells. Genistein, an inhibitor of protein tyrosine kinases, which by itself had little effect on choline formation, significantly suppressed the formation of choline induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of PKC, in a dose-dependent manner. Tyrphostin, an inhibitor of protein tyrosine kinases chemically distinct from genistein, also dose-dependently suppressed the TPA-induced formation of choline. Sodium orthovanadate, an inhibitor of protein tyrosine phosphatases, significantly enhanced the TPA-induced formation of choline in a dose-dependent manner. These results strongly suggest that protein tyrosine kinase regulates phospholipase D activity at a point downstream from PKC in osteoblast-like cells.

3T3 Cells↗
PubMed1995

Glucocorticoid amplifies vasopressin-induced phosphoinositide hydrolysis in aortic smooth muscle cells.

It has been reported that glucocorticoid modifies phosphoinositide (PI) hydrolysis stimulated by vasoactive agents in vascular smooth muscle cells. In the present study, we investigated the point at which glucocorticoid affects vasopressin-induced PI hydrolysis in primary cultured rat aortic smooth muscle cells. The pretreatment with dexamethasone significantly amplified the formation of inositol trisphosphate (IP3) induced by vasopressin in a dose-dependent manner in a range of 1 pM to 10 nM. The effect of dexamethasone was dependent on the time of pretreatment up to 8 h. Dexamethasone had little effect on the number of vasopressin receptor and its affinity to vasopressin. The pretreatment with dexamethasone also amplified the formation of IP3 induced by NaF, a GTP-binding protein activator, or angiotensin II. 12-O-Tetradecanoylphorbol-13-acetate, a protein kinase C (PKC)-activating phorbol ester, significantly reduced the dexamethasone-induced enhancement of IP3 formation stimulated by vasopressin, angiotensin II or NaF 4 alpha-Phorbol-12, 13-didecanoate, a PKC-nonactivating phorbol ester, had little effect on the enhancement by dexamethasone. These results strongly suggest that glucocorticoid amplifies vasopressin-induced PI hydrolysis at a point downstream from GTP-binding protein in primary cultured rat aortic smooth muscle cells, and that the activation of PKC has a negative feedback effect on the amplification by glucocorticoid of vasopressin-induced PI hydrolysis.

Animals↗
PubMed1995

Mechanism of phospholipase D activation induced by prostaglandin D2 in osteoblast-like cells: function of Ca2+/calmodulin.

Prostaglandin D2 (PGD2) stimulated the formation of choline in a dose-dependent manner in the range between 10 nM and 10 microM. The effect of PGD2 on the formation of inositol phosphates (EC50 was 20 nM) was more potent than that on the formation of choline (EC50 was 0.5 microM). The formation of choline stimulated by a combination of PGD2 and 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, was additive. Staurosporine, an inhibitor for protein kinases, enhanced the PGD2-induced formation of choline, but H-7, another inhibitor for protein kinases, had little effect. PGD2 stimulated Ca2+ influx from extracellular space dose-dependently. The depletion of extracellular Ca2+ by EGTA reduced the PGD2-induced formation of choline. W-7 and trifluoperazine dihydrochloride, antagonists of calmodulin, dose-dependently inhibited the PGD2-induced choline formation. These results strongly suggest that PGD2 activates phospholipase D in a Ca2+/calmodulin dependent manner in osteoblast-like cells, and that protein kinase C is not essential for the PGD2-induced activation of phospholipase D.

Animals↗
PubMed1995

Genistein inhibits potentiation by wortmannin of protein kinase C-activated phospholipase D in osteoblast-like cells.

We previously showed that protein kinase C (PKC) induces phosphatidylcholine-hydrolysing phospholipase D activation in osteoblast-like MC3T3-E1 cells and that tyrosine kinase is involved in this activation. Wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase, markedly enhanced the formation of choline induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of PKC in MC3T3-E1 cells. The effect of wortmannin was dose-dependent between 0.1 microM and 10 microM. ML-7, an inhibitor of myosin light chain kinase, had little effect on the TPA-induced formation of choline. Genistein, an inhibitor of protein tyrosine kinases, significantly suppressed the potentiation by wortmannin. These results strongly suggest that phosphatidylinositol 3-kinase is involved in the regulation of phospholipase D activation by PKC in osteoblast-like cells.

3T3 Cells↗
PubMed1995

Function of Ca2+ influx in phospholipase D activation induced by prostaglandin F2 alpha in osteoblast-like cells: involvement of tyrosine kinase.

We previously reported that prostaglandin F2 alpha (PGF2 alpha) induces Ca2+ influx from the extracellular space via protein tyrosine kinase in osteoblast-like MC3T3-E1 cells and that PGF2 alpha stimulates phosphatidylcholine-hydrolyzing phospholipase D in these cells (6, 12). In this study, we examined the relationship between the tyrosine kinase-regulated Ca2+ influx by PGF2 alpha and the activation of phospholipase D in MC3T3-E1 cells. The depletion of extracellular Ca2+ by [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA) markedly reduced the PGF2 alpha-induced formation of choline. Genistein, an inhibitor of protein tyrosine kinases, which by itself had little effect on choline formation, significantly suppressed the formation of choline induced by PGF2 alpha in a dose-dependent manner. Tyrphostin, an inhibitor of protein tyrosine kinases chemically distinct from genistein, also suppressed the PGF2 alpha-induced formation of choline. Sodium orthovanadate, an inhibitor of protein tyrosine phosphatases, significantly enhanced the PGF2 alpha-induced formation of choline. These results strongly suggest that the phospholipase D activation by PGF2 alpha is dependent on extracellular Ca2+ in osteoblast-like cells and that protein tyrosine kinase is involved in the activation of phospholipase D.

Animals↗
PubMed1995

Thromboxane A2-stimulated phospholipase D in osteoblast-like cells: possible involvement of PKC.

We examined the effect of thromboxane A2 (TxA2) on phosphatidylcholine-hydrolyzing phospholipase D activity in osteoblast-like MC3T3-E1 cells. 9,11-Epithio-11,12-methanothromboxane A2 (STA2), a stable analogue of TxA2, stimulated the formations of both choline and inositol phosphates in a dose-dependent manner in the range between 10 nM and 10 microM. The formation of choline stimulated by a combination of STA2 and 12-O-tetradecanoylphorbol 13-acetate (TPA), a protein kinase C-activating phorbol ester, was not additive. 1-(5-Isoquinolinyl-sulfonyl)-2-methylpiperazine (H-7), an inhibitor of protein kinases, suppressed the formation of choline induced by STA2 as well as that by TPA, but 20 microM N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA-1004), a control for H-7 as a protein kinase C inhibitor, had little effect. Calphostin C, a potent and specific inhibitor of protein kinase C, also suppressed the formation of choline induced by STA2. The STA2-induced formation of choline was significantly reduced by chelating extracellular Ca2+ with ethylene glycol-bis(beta-amino-ethyl ether)-N,N,N',N'-tetraacetic acid. STA2 dose dependently stimulated 45Ca2+ influx from extracellular space. STA2 stimulated DNA synthesis of MC3T3-E1 cells and increased the number of these cells. These results suggest that TxA2 stimulates phospholipase D in osteoblast-like cells, resulting in the direction of their proliferation, and that the activation of protein kinase C is involved in the stimulation of phospholipase D.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Effect of platelet-derived growth factor on phosphatidylcholine-hydrolyzing phospholipase D in osteoblast-like cells.

We examined the effect of platelet-derived growth factor (PDGF) on the activation of phosphatidylcholine-hydrolyzing phospholipase D in osteoblast-like MC3T3-E1 cells. PDGF-BB stimulated both the formation of choline (EC50 = 15 ng/ml) and inositol phosphates (EC50 = 5 ng/ml). However, PDGF-BB had little effect on the formation of phosphocholine. The formation of choline stimulated by a combination of PDGF-BB and 12-O-tetradecanoylphorbol-13-acetate, a protein kinase C (PKC)-activating phorbol ester, was additive. H-7, an inhibitor of protein kinases, inhibited 12-O-tetradecanoylphorbol-13-acetate-induced choline formation, whereas HA1004, a control for H-7 as PKC inhibitor, had little effect. Neither H-7 nor HA1004 affected the PDGF-BB-induced formation of choline. Genistein and methyl 2,5-dihydroxycinnamate, inhibitors of protein tyrosine kinases, dose dependently inhibited the PDGF-BB-induced formation of choline. PDGF-BB stimulated Ca2+ influx from extracellular space. PDGF-BB-induced choline formation was significantly reduced by chelating extracellular Ca2+ with EGTA. PDGF-BB stimulated DNA synthesis of MC3YT3-E1 cells, and H-7 inhibited the DNA synthesis. These results strongly suggest that PDGF activates phosphatidyl-choline-hydrolyzing phospholipase D independently from PKC activated by phosphoinositide hydrolysis in osteoblast-like cells, and that both tyrosine kinase activation and Ca2+ influx are essential for this mechanism.

Animals↗
PubMed1995

Gene amplification as a cause of inherited thyroxine-binding globulin excess in two Japanese families.

T4-binding globulin (TBG) is the major thyroid hormone transport protein in man. Inherited abnormalities in the level of serum TBG have been classified as partial deficiency, complete deficiency, and excess. Sequencing analysis of the TBG gene, located on Xq21-22, has uncovered the molecular defects causing partial and complete deficiency. However, the mechanism leading to inherited TBG excess remains unknown. In this study, two Japanese families, F-A and F-T, with inherited TBG excess were analyzed. Serum TBG levels in hemizygous males were 58 and 44 micrograms/mL, 3- and 2-fold the normal value, respectively. The molecule had normal properties in terms of heat stability and isoelectric focussing pattern. The sequence of the coding region and the promoter activity of the TBG gene were also indistinguishable between hemizygotes and normal subjects. The gene dosage of TBG relative to that of beta-globin, which is located on chromosome 11, and Duchenne muscular dystrophy, which is located on Xp, was evaluated by coamplification of these target genes using polymerase chain reaction and subsequent quantitation by HPLC. The TBG/beta-globin ratios of the affected male and female of F-A were 3.13 and 4.13 times, respectively, that in the normal males. The TBG/Duchenne muscular dystrophy ratios were 2.92 and 2.09 times the normal value, respectively. These results are compatible with three copies of TBG gene on the affected X-chromosome. Similarly, a 2-fold increase in gene dosage was demonstrated in the affected hemizygote of F-T. A 3-fold tandem amplification of the TBG gene was shown by in situ hybridization of prometaphase and interphase chromosomes from the affected male with a biotinylated genomic TBG probe, confirming the gene dosage results. Gene amplification of TBG is the cause of inherited TBG excess in these two families.

Base Sequence↗
PubMed1995

Two novel mutations in the coding region for neurophysin-II associated with familial central diabetes insipidus.

Familial central diabetes insipidus is an autosomal dominant disease caused by a deficiency of arginine vasopressin (AVP). We previously reported three distinct mutations in the AVP gene in Japanese familial central diabetes insipidus pedigrees that result in a substitution of Ser for Gly57 in the neurophysin-II (NPII) moiety of the AVP precursor, a substitution of Thr for Ala at the COOH-terminus of the signal peptide, and a deletion of Glu47 in the NPII moiety. In this study, we analyzed the AVP gene in two pedigrees by direct sequencing of the polymerase chain reaction-amplified DNA and found two novel mutations in exon 2, which encodes the central part of the NPII moiety of the precursor. The mutation in one pedigree was a C to A transition at nucleotide position 1891, which replaces Cys67 (TGC) with stop codon (TGA). As the premature termination eliminates part of the COOH domain of the NPII moiety and the glycoprotein moiety, the conformation of the truncated protein is likely to be markedly different from that of normal precursor. In another pedigree, a G to T transversion was detected at nucleotide position 1874, which substitutes polar Trp (TGG) for hydrophobic Gly62 (GGG). It is possible that mutated NPII molecules, as a consequence of a conformational change, cannot bind AVP or self-associate to form higher oligomer complexes. Interestingly, all mutations we have identified to date, with the exception of the signal peptide mutation, are located in exon 2, suggesting the importance of the highly conserved central part of the NPII molecules and/or the NPII moiety in the precursor for AVP synthesis.

Adolescent↗
PubMed1995

Mechanism of phospholipase D activation induced by extracellular ATP in osteoblast-like cells.

We have previously reported that extracellular ATP stimulates Ca2+ influx from extracellular space, resulting in the production of prostaglandin E2 which mediates, at least in part, its proliferative effect on osteoblast-like MC3T3-E1 cells, and that the activation of protein kinase C (PKC) stimulates phospholipase D in these cells. In the present study, we examined the effect of extracellular ATP on phosphatidylcholine-hydrolysing phospholipase D activity in MC3T3-E1 cells. ATP stimulated the formation of both choline and inositol phosphates dose-dependently in the range between 0.1 and 1 mM. The formation of choline by a combination of ATP and NaF, an activator of GTP-binding protein, was synergistic, whereas that of inositol phosphates was not. A combination of ATP and 12-O-tetradecanoylphorbol-13-acetate, a PKC activating phorbol ester, additively stimulated the formation of choline. Staurosporine, an inhibitor of PKC, had little effect on ATP-stimulated formation of choline. Choline formation was significantly reduced by chelating extracellular Ca2+ with EGTA, while being inhibited by W-7, an antagonist of calmodulin. These results suggest that extracellular ATP stimulates phospholipase D in a Ca2+/calmodulin-dependent manner in osteoblast-like cells, and that neither PKC activation nor GTP-binding protein is involved in this mechanism.

Adenosine Triphosphate↗
PubMed1995

A case of primary glucocorticoid resistance.

A 79-year-old woman developed hypokalemia and metabolic alkalosis after breast cancer surgery. She was suspected of having primary glucocorticoid resistance on the basis of high plasma ACTH and serum cortisol levels without the features of Cushing's syndrome. To clarify the end-organ resistance to cortisol, we characterized the glucocorticoid receptors (GR) in cultured skin fibroblasts from the patient. The GRs in whole cell assays decreased binding affinity (Kd = 11.1 +/- 0.6 nM) and the number of binding sites for [3H]dexamethasone (binding capacity was 15,600 +/- 1,255 sites per cell). These results strongly suggest that our patient had primary glucocorticoid resistance caused both by a decreased number of GRs and a reduction in the affinity of GRs to cortisol.

Aged↗
PubMed1994

Glucocorticoid inhibits cAMP production induced by vasoactive agents in aortic smooth muscle cells.

It is well-known that atherosclerotic change and hypertension are common manifestations in patients with glucocorticoid excess. We previously reported that pituitary adenylate cyclase activating polypeptide (PACAP), prostaglandin E2 (PGE2) and carbacyclin, a stable analog of prostacyclin, have suppressive effects on vasopressin-induced DNA synthesis of rat aortic smooth muscle cells through cAMP production (Murase et al., J. Hypertens., 10 (1992) 1505; Oiso et al., Biochem. Cell. Biol., 71 (1993) 156). In the present study, we investigated the effect of glucocorticoid on cAMP production induced by PACAP, PGE2 and carbacyclin in aortic smooth muscle cells. The pretreatment with dexamethasone significantly inhibited cAMP accumulation induced by these vasoactive agents in a dose dependent manner in the range between 10 pM and 10 nM. These inhibitory effects of dexamethasone were dependent on the time of pretreatment up to 8 h. Dexamethasone inhibited cAMP accumulation induced by NaF, a GTP-binding protein activator, and forskolin which directly activates adenylate cyclase. Moreover, forskolin-induced adenylate cyclase activity was significantly reduced in membranes prepared from the cells treated with dexamethasone. These results strongly suggest that glucocorticoid inhibits cAMP production induced by vasoactive agents in primary cultured rat aortic smooth muscle cells and the inhibitory effect is exerted at the level of adenylate cyclase.

Animals↗
PubMed1994

Effect of prostaglandin F2 alpha on Ca2+ influx in osteoblast-like cells: function of tyrosine kinase.

We previously reported that pertussis toxin-sensitive GTP-binding protein is involved in prostaglandin F2 alpha (PGF2 alpha)-induced phosphoinositide (PI) hydrolysis in osteoblast-like MC3T3-E1 cells [Miwa et al. (1990): Biochem Biophys Res Commun 171:1229-1235]. In the present study, we investigated the mechanism of PGF2 alpha-induced Ca2+ influx in MC3T3-E1 cells. PGF2 alpha-induced formation of total inositol phosphates (IPs) was markedly reduced by the depletion of extracellular Ca2+ with EGTA. On the other hand, the depletion of extracellular Ca2+ had little effect on PGF2 alpha-induced inositol 1,4,5-trisphosphate formation. PGF2 alpha stimulated 45Ca2+ influx dose dependently, attaining a maximum effect at 10 nM. Dose of PGF2 alpha above 10 nM caused less than maximal stimulation. Genistein, an inhibitor of protein tyrosine kinase, which by itself had little effect on 45Ca2+ influx, significantly suppressed the PGF2 alpha-induced 45Ca2+ influx in a dose-dependent manner in the range between 1 micrograms/ml and 0.1 mg/ml. Sodium orthovanadate, an inhibitor of protein tyrosine phosphatases, enhanced the PGF2 alpha-induced 45Ca2+ influx. Genistein also suppressed the PGF2 alpha-induced total IPs formation dose dependently in the range between 1 micrograms/ml and 0.1 mg/ml. However, it had little effect on the PGF2 alpha-induced inositol 1,4,5-trisphosphate formation. The pretreatment with pertussis toxin had little effect on the PGF2 alpha-induced 45Ca2+ influx. These results strongly suggest that PGF2 alpha stimulates Ca2+ mobilization from extracellular space and PI hydrolysis via independent pathways in osteoblast-like cells, and the PGF2 alpha-induced Ca2+ influx is regulated by protein tyrosine kinase, resulting in the promotion of PI hydrolysis.

Calcium↗