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H Hidaka

Publications and source records attributed to H Hidaka.

At least 181 records · Page 10Linked to original sources

Ca2+ signaling and intracellular Ca2+ binding proteins.

Changes in cytosolic Ca2+ concentrations evoke a wide range of cellular responses and intracellular Ca(2+)-binding proteins are the key molecules to transduce Ca2+ signaling via enzymatic reactions or modulation of protein/protein interations (Fig.1). The EF hand proteins, like calmodulin and S100 proteins, are considered to exert Ca(2+)-dependent actions in the nucleus or the cytoplasm. The Ca2+/phospholipid binding proteins are classified into two groups, the annexins and the C2 region proteins. These proteins, distributed mainly in the cytoplasm, translocate to the plasma membrane in response to an increase in cytosolic Ca2+ and function in the vicinity of the membrane. Ca2+ storage proteins in the endoplasmic or sarcoplasmic reticulum provide the high Ca2+ capacity of the Ca2+ store sites, which regulate intracellular Ca2+ distribution. The variety and complexity of Ca2+ signaling result from the cooperative actions of specific Ca(2+)-binding proteins. This review describes biochemical properties of intracellular Ca(2+)-binding proteins and their proposed roles in mediating Ca2+ signaling.

Animals↗

Traumatic rupture of hepatic hemangioma.

Although hepatic hemangioma is common, its rupture after trauma is rare. We report a 47-year-old woman with a traumatic hepatic hemangioma rupture following a traffic accident who successfully underwent operation. Only four cases of hepatic hemangioma rupture caused by blunt trauma have been reported including this one. Each patient (two men and two women) had a giant right lobe hemangioma. The causal injury included a traffic accident in two, a fall in one, and minor trauma in another. Three patients underwent surgery, and one was conservatively managed. All the patients survived.

Female↗

Neuroprotective properties of a protein kinase inhibitor against ischaemia-induced neuronal damage in rats and gerbils.

1. The neuroprotective properties of fasudil (HA1077), a novel protein kinase inhibitor, were evaluated in two animal models of cerebral ischaemia: transient bilateral carotid artery occlusion in Mongolian gerbils and cerebral microembolization in rats. 2. The cytoprotective effect of fasudil on delayed neuronal death in gerbils was compared with the effects of nimodipine, a calcium channel antagonist and ozagrel, a thromboxane A2 synthetase inhibitor. The average of the neuronal cell density in the ischaemic control group was 17.8 +/- 2.1 cells mm-1, whereas fasudil (30 mg kg-1) significantly diminished the loss of CA1 neurones with the average of the neuronal cell density of 101.0 +/- 22.0 cells mm-1; nimodipine (10 mg kg-1) and ozagrel (30 mg kg-1) did not significantly protect against the ischaemia-induced neuronal loss. 3. In the rat model, the effects of fasudil on the histological and neurological consequences of cerebral microembolization produced via the injection of microspheres were examined. Twenty-four hours after the injection of microspheres into the internal carotid artery, all animals in the control group showed typical symptoms of stroke. Neurological function was significantly improved in the fasudil-treated animals. In the controls, the infarcted area in a cortical slice selected to include the hippocampal area was 0.25 +/- 0.01 cm2 (mean +/- s.e.mean) (43.9 +/- 2.4% of cortical section of the half hemisphere); the difference was significant compared to the mean area of 32.7 +/- 2.8 and 21.5 +/- 4.8% observed in rats treated with fasudil (3, 10 mg kg-1), respectively. Fasudil (10 mg kg-1) significantly suppressed the increased water content in ischaemic brain tissues (saline-treated rats, 82.4 +/- 0.2% vs fasudil-treated rats, 81.0 +/- 0.4%). 4. These results suggest that: (i) various protein kinases are involved in the pathogenesis of ischaemic injury; and (ii) the inhibition of protein kinases may be efficacious in preventing neuronal death, thus improving neurological function in the brain damage associated with ischaemic stroke.

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

Hyaline cartilage: in vivo and in vitro assessment with magnetization transfer imaging.

PURPOSE: To elucidate the magnetization transfer (MT) effects of major components of hyaline cartilage. MATERIALS AND METHODS: The authors evaluated the MT effect of type II collagen and chondroitin sulfate phantoms (concentrations of 0.6%, 1.2%, 2.4%, 4.8%, 9.6%, and 19.2%), mass-cultured rat osteosarcoma-derived cells, and normal articular cartilage of the knee. RESULTS: The MT effect of collagen yielded a decrease in signal intensity of 10% (1.2% collagen) to 31% (19.2% collagen); the decrease varied linearly with collagen concentration. Chondroitin sulfate did not have a statistically significant MT effect. Cell pellets showed a decrease in signal intensity of 22%-26%, which was greater than that of 4.8% collagen. Normal articular cartilage of the knees showed a decrease in signal intensity of 38%-48%. CONCLUSION: The major role of collagen in MT contrast of hyaline cartilage was confirmed. In addition, a higher cellular contribution to the MT effect was also demonstrated.

Adolescent↗

Insulin signaling and its regulation of system A amino acid uptake in cultured rat vascular smooth muscle cells.

Hyperinsulinemia has been recognized as an independent risk factor for atherosclerosis. However, its exact mechanisms are still unclear. In our previous work, we showed that 10 nmol/L insulin stimulated neither mitogen-activated protein kinase (MAP kinase) activity nor [3H]thymidine incorporation but did stimulated S6 kinase through the specific insulin receptors in cultured rat vascular smooth muscle cells (VSMCs). In this study, we observed that > or = 1 nmol/L insulin stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and activated IRS-1-dependent phosphatidylinositol 3'-kinase (PI 3'-kinase) and p70 S6 kinase (p70S6K) but not MAP kinase (extracellular signal-regulated kinase 2) and p90 S6 kinase (p90RSK). However, 10 nmol/L insulin-like growth factor I stimulated all these pathways. Finally, 10 nmol/L insulin stimulated alpha-amino-isobutyric acid (AIB) uptake, and wortmannin (100 nmol/L) completely inhibited insulin-stimulated AIB uptake, whereas rapamycin (20 nmol/L) had no such effect. Furthermore, cycloheximide (10 micrograms/mL) completely inhibited insulin-stimulated AIB uptake, but actinomycin D (5 micrograms/mL) failed to inhibit this. Thus, we reached the following conclusions: (1) Insulin (1 nmol/L) induced phosphorylation of IRS-1 and activated the PI 3'-kinase and p70S6K pathways in VSMCs, even though 10 nmol/L insulin did not significantly stimulate MAP kinase or p90RSK. (2) Stimulation of AIB uptake by insulin was regulated at the translational level via wortmannin-sensitive pathways but not p70S6K pathways.

Aminoisobutyric Acids↗

Ca2+/calmodulin and cyclic 3,5' adenosine monophosphate control movement of secretory granules through protein phosphorylation/dephosphorylation in the pancreatic beta-cell.

We observed the movement of insulin granules in living transformed hamster pancreatic beta-cells (HIT T15) with a light microscope, where secretory granules are moving in the cytoplasmic space. Velocity of the typical granule movement was approximately 1.5 microns/sec. A stimulatory concentration of glucose activated the movement of the secretory granules. Forskolin, an activator of adenylate cyclase, increased the movement, resulting in changes in intracellular localization of the granules. Acetylcholine also activated the granule movement, whereas high K+ and tolbutamide, which cause Ca2+ influx through the voltage-dependent Ca2+ channel, had only little effect. The movement was abolished by BAPTA, the intracellular Ca2+-chelator. Activation of protein kinase C by 12-O-tetradecanoyl-phorbol 13-acetate failed to affect this movement. The motile events were inhibited by the calmodulin antagonist, W-7, and dramatically increased by okadaic acid, an inhibitor of protein phosphatases 1 and 2A. These results suggest protein phosphorylation by Ca2+/calmodulin- and cAMP-dependent protein kinases play a positive role in the control of the insulin granule movements, which results in potentiation of insulin release from the pancreatic beta-cell.

Acetylcholine↗

Inhibition of P-glycoprotein-dependent multidrug resistance by an isoquinolinesulfonamide compound H-87 in rat ascites hepatoma AH66 cells.

The effects of an isoquinolinesulfonamide compound, H-87, on naturally acquired multidrug-resistance (MDR) in rat hepatoma AH66 cells were examined. AH66 cells were highly resistant to vinblastine, SN-38, an active camptothecin analog, adriamycin, and etoposide, compared with the sensitive variant AH66F cells. Although H-87 hardly affected the sensitivities to antitumor agents of AH66F cells, this compound completely inhibited the resistance to vinblastine, moderately inhibited the resistance to SN-38 and adriamycin and had little effect on etoposide, mitomycin C, cisplatin, and 5-fluorouracil. H-87 significantly decreased the efflux of vinblastine from the resistant cells and increased the drug accumulation. SN-38 and adriamycin also exhibited a weak but significant increase in vinblastine accumulation in AH66 cells. H-87 inhibited [3H]azidopine-photolabeling to 160 kDa P-glycoprotein in the plasma membrane of AH66 cells, as reported in acquired MDR leukemic cells. Consequently, the MDR-overcoming effect of H-87 seems to be due to its direct inhibition of the binding of antitumor agents on P-glycoprotein in the plasma membrane.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

HMN-709, a chlorobenzenesulfonamide derivative, is a new membrane-permeable calmodulin antagonist.

Our objective is to describe the basic chemical and biological properties of the new calmodulin antagonist HMN-709 (2-[N-(2-aminoethyl)-N-(4-chlorobenzenesulfonyl)]amino-N-(4-flu orocinnamyl)-N-methylbenzylamine). This newly synthesized compound was found to inhibit the Ca2+/calmodulin-dependent activation of calmodulin kinase I, smooth muscle myosin light chain kinase and Ca2+-phosphodiesterase with IC50 values of 1.57+/-0.21, 2.29+/-0.09 and 0.30+/-0.08 microM (mean+/-S.E.), respectively. This compound showed little or no effect on the Ca2+/calmodulin-independent activation of protein kinase A, protein kinase C and basal phosphodiesterase. In addition, HMN-709 inhibited calmodulin kinase I competitively with respect to calmodulin (Ki=0.88 microM) and non-competitively with respect to ATP. Affinity chromatography, with HMN-709-coupled Sepharose HP, showed that the compound bound to calmodulin in a Ca(2+)-dependent manner and did not bind to calmodulin kinase I. These results suggest that HMN-709 antagonizes calmodulin by binding to Ca2+/calmodulin. HMN-709 inhibited collagen-induced platelet aggregation with an IC50 value of 11.80+/-0.86 microM (mean+/-S.E.) without inhibiting phorbol 12,13-dibutyrate-induced aggregation at doses up to 12 microM. HMN-709 appears to be a new, membrane-permeable calmodulin antagonist that may be used for studying the involvement of calmodulin in cellular processes.

Animals↗

Multiple endocrine neoplasia type 1 associated with malignant lymphoma and other complications.

A 49-year-old female with multiple endocrine neoplasia (MEN) type 1 associated with malignant lymphoma, lipoma, functioning adenomatous goiter, non-functioning adrenal tumor, polyneuropathy, postoperative primary hyperparathyroidism, and hepatitis B virus was a human T lymphotropic virus type 1 (HTLV-1) carrier. She underwent parathyroidectomy for primary hyperparathyroidism at age 44. At age 49, examinations of the enlarged para-aortic lymph nodes revealed diffuse small non-cleaved B cell lymphoma in stage II, and other various complications were also found. Multiple tumorigenetic factors were considered to be involved in the present case.

Adrenal Gland Neoplasms↗

[Accurate placement of central venous catheters using right atrial electrocardiography].

We have evaluated the effectiveness of central venous catheter placement using right atrial electrocardiography (RAECG). Consecutive patients under general anesthesia (n = 42) who required a central venous catheter underwent RAECG-guided catheter insertion procedure via right internal jugular vein. Catheter tip position was verified by post procedure portable chest radiography. Forty of 42 catheter tips were placed above the superior vena cava-right atrial junction, and none of them had its associated complications. The average insertion depth of catheters was 16.4 cm. We also attempted to predict the optimal catheter insertion depth for each patient from the previous measurements of external landmarks, but it was found to be difficult to predict reliably. In this point of view, we should use RAECG technique to make sure the proper positioning of the catheter tip.

Aged↗

[Two cases of liver scar that was examined by biliary scintigraphy].

36-year-old-female admitted because of jaudice and ascites. T-bil was 18.5 mg/dl and transaminase, ALP, LDH and gamma-GTP was elevated. Ultrasonography (US) showed that right lobe was atrophy and left lobe was swelling. Plain computed tomography (CT) showed right lobe was low density. Magnetic resonance (MR) finding was T1-weighted image of right lobe was low intensity and T2-weighted image was high intensity. Angiography showed right lobe was more stained than left lobe. Histologically, right lobe was massive necrosis. These findings suggested that right lobe was liver scar. Biliary imaging showed right lobe was delayed. A 23-year-old-female admitted because of fever and abdominal tumor. Transaminase was normal, only gamma-GTP was elevated. US, plain CT, enhanced CT, MR imaging finding was as same as that of the first case. Similarily, biliary scintigraphy showed right lobe was delayed. Causes of the two liver scars was not clear, whereas liver scar detected after delivery was rare case.

Adult↗

Anti-immunoglobulin M activates nuclear calcium/calmodulin-dependent protein kinase II in human B lymphocytes.

We and others have previously shown that the nuclear protein, Ets-1, is phosphorylated in a calcium-dependent manner after ligation of immunoglobulin (Ig) M on B lymphocytes. As this phosphorylation was independent of protein kinase C activity, we tested whether a calcium/calmodulin-dependent protein kinase (CaM kinase) might phosphorylate the Ets-1 protein after elevation of intracellular free calcium concentrations. The dephosphorylated form of Ets-1 has been shown to bind to chromatin, suggesting that the operative kinase should be detectable in the nucleus. We prepared nuclear extracts from two human B cell lines in which increased intracellular free calcium levels correlated with increased phosphorylation of the Ets-1 protein. Activity of the CaM kinases was determined using a synthetic peptide substrate both in the absence and presence of an inhibitor specific for the CaM kinase family, KN-62. Stimulation of cells with anti-IgM led to increased activity of a nuclear kinase that could phosphorylate the peptide, and this activity was reduced by 10 microM KN-62. Kinase activity was reduced in lysates preadsorbed using an antibody specific for CaM kinase II. Two-dimensional phosphopeptide maps of the Ets-1 protein from cells incubated with ionomycin or anti-IgM contained two unique phosphopeptides that were absent in untreated cells. Incubation of isolated Ets-1 protein with purified CaM kinase II produced phosphorylation of peptides that migrated identically to those found in cells incubated with either anti-IgM or ionomycin. These data suggest a model of signal transduction by the antigen receptor on B lymphocytes in which increased intracellular free calcium can rapidly activate nuclear CaM kinase II, potentially resulting in phosphorylation and regulation of DNA-binding proteins.

Amino Acid Sequence↗

Purification and characterization of a novel protein activator of Ca2+/calmodulin-dependent protein kinase I.

A protein activator of Ca2+/calmodulin (CaM)-dependent protein kinase I was purified from rat brain. The activator was retained on a CaM-Sepharose column in the presence of Ca2+ and kinase assay of renatured gel revealed the 64 kDa molecule in the purified activator fraction to be autophosphorylated and to phosphorylate recombinant CaM kinase I in the presence of Ca2+/calmodulin. These results suggest that this activator of CaM kinase I is also a CaM-dependent protein kinase. Phosphorylation of CaM kinase I by the activator resulted in drastic potentiation of its CaM-dependent activity. Furthermore, kinetic analyses demonstrated that the activation decreases the Km values of CaM kinase I for both ATP and syntide-2 without a change in Vmax values. Considering the quite low enzymatic activity of recombinant CaM kinase I without activation, the 64 kDa species might be essential for CaM kinase I function in vivo.

Adenosine Triphosphate↗

Effect of KN-62, Ca2+/calmodulin-dependent protein kinase II inhibitor, on adriamycin resistance of human ovarian cancer cells.

We examined effects of an isoquinolinesulfonamide derivative, KN-62, on human ovarian cancer cells, NOS3AR, that are resistant to Adriamycin (ADR). MTT assay revealed that 10 microM KN-62 overcame the resistance. KN-62 had little effect on GST activity. In studies on the intracellular accumulation of ADR, KN-62 increased the ADR contents in the resistant cells close to the level seen in the sensitive cells. These results suggest that the reversal of the resistance against ADR in ovarian cancer cells by KN-62 is mainly due to higher accumulation of ADR in NOS3AR cells. Furthermore, we detected Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) in NOS3AR cells since KN-62 is a specific inhibitor of the kinase. In this paper, we discussed on modulation of ADR-resistance by KN-62.

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

The regulatory region of calcium/calmodulin-dependent protein kinase I contains closely associated autoinhibitory and calmodulin-binding domains.

The mechanism for the regulation of Ca2+/calmodulin-dependent protein kinase I (CaM kinase I) was investigated using a series of COOH-terminal truncated mutants. These mutants were expressed in bacteria as fusion proteins with glutathione S-transferase and purified by affinity chromatography using glutathione Sepharose 4B. A mutant (residues 1-332) showed complete Ca2+/CaM-dependent activity. Truncation mutants (residues 1-321, 1-314, and 1-309) exhibited decreasing affinities for Ca2+/CaM and also exhibited decreasing Ca2+/CaM-dependent activities. Truncation mutants (residues 1-305 or 1-299) were unable to bind Ca2+/CaM and were inactive. In contrast, truncation mutants (residues 1-293 or 1-277) were constitutively active at a slightly higher level (2-fold) than fully active CaM kinase I. These results indicate the location of the Ca2+/CaM-binding domain on CaM kinase I (residues 294-321) and predict the existence of an autoinhibitory domain near, or overlapping, the Ca2+/CaM-binding domain. These conclusions were supported by studies which showed that a synthetic peptide (CaM kinase I (294-321)) corresponding to residues 294-321 of CaM kinase I inhibited the fully active kinase in a manner that was competitive with Ca2+/CaM and also inhibited the constitutively active mutant (residues 1-293) in a manner that was competitive with Syntide-2, a peptide substrate, (Ki = 1.2 microM) but was non-competitive with ATP. Thus, these results suggest that CaM kinase I is regulated through an intrasteric mechanism common to other members of the family of Ca2+/CaM-dependent protein kinases.

Amino Acid Sequence↗

Estrogen increases endothelial nitric oxide by a receptor-mediated system.

To determine the mechanism of the antiatherosclerotic effect of estrogen, we investigated the effect of estrogen on endothelial nitric oxide synthase (NOS-3). Preincubation with a physiologic concentration of 17 beta-estradiol (10(-12)-10(-8) M) over 8 hours significantly enhanced the activity of NOS-3 in endothelial cells of cultured human umblical vein (HUVEC) and of bovine aortas (BAEC). 17 beta-estradiol also enhanced the release of nitric oxide (NO) as measured by an NO selective meter and NO2-/NO3-, metabolites of NO, from endothelial cells. Western blot showed a similar effect of 17 beta-estradiol on NOS-3. The estrogen receptor antagonists, tamoxifen and ICI182780, each inhibited the effect of 17 beta-estradiol by 80%. The effect of 17 beta-estradiol gradually decreased in cells beyond the 10th passage and was not significant in cells beyond the 16th passage. Immunocytochemistry showed the existence of estrogen receptor in HUVEC and BAEC (less than 5 passages) and the sparseness of the existence in BAEC beyond the 16th passage. Estrogen increases NOS-3 via a receptor-mediated system, and estrogen receptor, which appeared to be altered by cell senescence, could be important in the release of NO from endothelium.

Animals↗