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1.
Oncogene ; 35(45): 5839-5849, 2016 11 10.
Article in English | MEDLINE | ID: mdl-27086928

ABSTRACT

Nedd4 (Nedd4-1) is an E3 ubiquitin ligase that belongs to the HECT family and comprises a C2-WW(n)-HECT domain architecture. Although it has been reported to regulate growth factor receptors and cellular signaling, its role in cancer development has been controversial, with some studies proposing that it promotes cancer while others suggest it inhibits tumor growth. Here, we tested the effect of Nedd4 on intestinal tumor formation and growth using Nedd4-knockout mice (Nedd4 floxed (fl) mice crossed to villin-Cre mice). Although we find that knockout of Nedd4 on its own does not cause tumor growth, its knockout in the context of Apc+/min-derived colorectal tumors leads to augmentation of tumor growth, suggesting that Nedd4 normally suppresses intestinal WNT signaling and growth of colonic tumors. WNT signaling microarray, immunoblotting and immunohistochemistry analyses of tumors derived from the Villin-Cre;Nedd4fl/fl;Apc+/min colons demonstrated elevated expression of the WNT upstream effectors LEF1 (full length) and YY1 in these tumors relative to control (Apc+/min alone) tumors. Together, these results suggest that Nedd4 suppresses colonic WNT signaling and tumor growth, at least in part, by suppressing the transcription factors LEF1 and YY1.


Subject(s)
Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Endosomal Sorting Complexes Required for Transport/deficiency , Genes, APC , Ubiquitin-Protein Ligases/deficiency , Animals , Biomarkers , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/metabolism , Colonic Neoplasms/metabolism , Disease Models, Animal , Endosomal Sorting Complexes Required for Transport/genetics , Endosomal Sorting Complexes Required for Transport/metabolism , Gene Expression , Gene Knockout Techniques , Genes, Reporter , Homozygote , Immunohistochemistry , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Intestines/pathology , Mice , Mice, Knockout , Models, Biological , Nedd4 Ubiquitin Protein Ligases , Neoplasm Grading , Signal Transduction , Tumor Burden , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , Wnt Signaling Pathway
2.
AJNR Am J Neuroradiol ; 31(10): 1903-10, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20813875

ABSTRACT

BACKGROUND AND PURPOSE: SWI is a new MR imaging method that maximizes sensitivity to magnetic susceptibility effects with phase information for visualizing small cerebral veins. The purpose of this study was to report the use of SWI in combination with DSC in examining related RCVD in patients with intracranial DAVFs. MATERIALS AND METHODS: Ten patients with angiographically confirmed DAVFs with RCVD underwent conventional MR imaging, SWI, and DSC. The ability of SWI to depict dilated cerebral veins was evaluated and then compared with DSC. The hemispheres of patients with DAVFs were grouped into affected (with RCVD) or nonaffected (without RCVD) categories by angiography. Four patients had bilaterally affected hemispheres. A total of 14 affected hemispheres in patients with DAVFs with RCVD were evaluated. RESULTS: SWI showed dilated cerebral veins on the surface of the brain in all (100%) of the 14 affected hemispheres in patients with DAVFs with RCVD and deep in the brain in 9 (64%). T2-weighted imaging showed prominent flow-voids on the surface of the brain in 10 (71%) of the 14 affected hemispheres in patients with DAVFs with RCVD and deep in the brain in 5 (36%). DSC showed increased cerebral blood volume in all of the 14 affected hemispheres. The SWI findings regarding dilated veins on the surface of the brain corresponded well with the areas of increased cerebral blood volume. CONCLUSIONS: SWI in combination with DSC could be used to characterize the presence of RCVD in patients with DAVFs.


Subject(s)
Central Nervous System Vascular Malformations/pathology , Cerebral Veins/pathology , Magnetic Resonance Imaging/instrumentation , Magnetic Resonance Imaging/methods , Aged , Blood Volume , Cerebral Angiography , Cerebral Cortex/blood supply , Cerebral Hemorrhage/pathology , Contrast Media , Female , Humans , Magnetic Resonance Angiography , Male , Middle Aged , Sensitivity and Specificity , Superior Sagittal Sinus/pathology
4.
AJNR Am J Neuroradiol ; 27(6): 1252-6, 2006.
Article in English | MEDLINE | ID: mdl-16775275

ABSTRACT

BACKGROUND AND PURPOSE: Retrograde cortical venous drainage (RCVD) is the most major risk factor for aggressive behavior of intracranial dural arteriovenous fistulas (DAVF). The purpose of this study was to assess the efficacy of relative cerebral blood volume (rCBV) map for RCVD in patients with DAVF. METHODS: Ten patients with angiographically proven DAVF with RCVD, 2 reference patients with DAVF without RCVD, and 10 control subjects underwent examinations with dynamic susceptibility contrast (DSC)-MR imaging. Four patients with DAVF with unilateral RCVD were evaluated, before and after treatment. The calculation of mean rCBV ratio was performed on a hemispheric basis. The mean rCBV ratio was defined as the value on one side (higher value side) divided by that on the other side (lower value side). RESULTS: In all patients with DAVF with RCVD, the rCBV map showed an increase in rCBV of the angiographically proved affected hemisphere. In 2 reference patients with DAVF without RCVD and all control subjects, the rCBV map showed no increase of rCBV. The mean rCBV ratio in patients with DAVF with RCVD was significantly higher than that of control subjects (P = .0002). Treatment response for RCVD was indicated by a decrease of CBV on the rCBV map and by a decrease of 22% in the mean rCBV ratio. CONCLUSIONS: Increased rCBV by DSC-MR correlated with RCVD in patients with DVAF. The assessment with rCBV for RCVD may be more quantitative than that with angiogram.


Subject(s)
Blood Volume , Central Nervous System Vascular Malformations/diagnosis , Cerebrovascular Circulation , Contrast Media , Magnetic Resonance Angiography , Aged , Blood Volume Determination , Central Nervous System Vascular Malformations/diagnostic imaging , Central Nervous System Vascular Malformations/physiopathology , Cerebral Angiography , Female , Humans , Male , Middle Aged
5.
J Biol Chem ; 276(51): 48350-5, 2001 Dec 21.
Article in English | MEDLINE | ID: mdl-11602598

ABSTRACT

Tight junctions (TJs) serve as a barrier that prevents solutes and water from passing through the paracellular pathway, and as a fence between the apical and basolateral plasma membranes in epithelial cells. TJs consist of transmembrane proteins (claudin, occludin, and JAM) and many peripheral membrane proteins, including actin filament (F-actin)-binding scaffold proteins (ZO-1, -2, and -3), non-F-actin-binding scaffold proteins (MAGI-1), and cell polarity molecules (ASIP/PAR-3 and PAR-6). We identified here a novel peripheral membrane protein at TJs from a human cDNA library and named it Pilt (for protein incorporated later into TJs), because it was incorporated into TJs later after the claudin-based junctional strands were formed. Pilt consists of 547 amino acids with a calculated M(r) of 60,704. Pilt has a proline-rich domain. In cadherin-deficient L cells stably expressing claudin or JAM, Pilt was not recruited to claudin-based or JAM-based cell-cell contact sites, suggesting that Pilt does not directly interact with claudin or JAM. The present results indicate that Pilt is a novel component of TJs.


Subject(s)
Membrane Proteins/metabolism , Tight Junctions/metabolism , Adaptor Proteins, Signal Transducing , Amino Acid Sequence , Animals , COS Cells , DNA, Complementary , Discs Large Homolog 1 Protein , Epithelial Cells/metabolism , Humans , Membrane Proteins/chemistry , Membrane Proteins/genetics , Molecular Sequence Data , Protein Binding , Proteins/metabolism , Sequence Homology, Amino Acid , Subcellular Fractions , Tight Junction Proteins , Two-Hybrid System Techniques
6.
Nihon Rinsho ; 59(5): 938-44, 2001 May.
Article in Japanese | MEDLINE | ID: mdl-11391995

ABSTRACT

In patients with hypertension and chronic renal parenchymal disease, BP should be controlled to 130/85 mmHg or lower (125/75 mmHg) in patients with proteinuria in excess of 1 g/day. Reducing dietary sodium (< 7 g/day) and protein (< 0.6-0.7 g/kg) helps control high BP and renal function in patients with renal insufficiency. As first antihypertensive drug, ACE inhibitors or long-acting Ca antagonists are recommended. In patients with renovascular hypertension, angioplasty is the first choice increasingly to be accompanied by stenting, and surgical revascularization is the next choice. As antihypertensive drugs, beta blockers, ACE inhibitors, and AII-receptor blockers are recommended. Hypertension accompanied by endocrine disease with adenoma or tumor is almost cured or improved by surgical removal. Spironolactone and Ca antagonists are used in patients with idiopathic aldosteronism (bilateral hyperplasia). Alpha and beta blockers are used in patients with pheochromocytoma during preoperative period.


Subject(s)
Hypertension/etiology , Hypertension/therapy , Adrenergic beta-Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Calcium Channel Blockers/therapeutic use , Central Nervous System Diseases/complications , Endocrine System Diseases/complications , Endocrine System Diseases/therapy , Humans , Hypertension/chemically induced , Hypertension, Renal/therapy , Practice Guidelines as Topic , Spironolactone/therapeutic use
7.
Clin Sci (Lond) ; 100(2): 145-50, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11171282

ABSTRACT

We and others have reported that serum leptin levels are positively correlated with body mass index (BMI), blood pressure and heart rate (HR) in cross-sectional clinical studies. However, only a few longitudinal studies have focused on the relationships between leptin, BMI and blood pressure. The present study was performed to elucidate the relationships between baseline serum leptin levels and 2-year changes in BMI, blood pressure, HR and metabolic parameters in 314 Japanese male adolescents aged 16-17 years and in 225 Japanese men aged 30-63 years. Height, weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), HR, fasting plasma glucose (FPG), serum lipids [total cholesterol (TC), triacylglycerols (TG), high-density-lipoprotein cholesterol (HDL-C) and low-density-lipoprotein cholesterol (LDL-C)], uric acid (UA), insulin and leptin levels were measured in the morning after an overnight fast. In the male adolescents, serum leptin levels in 1996 (log[leptin'96]) were significantly correlated with BMI, SBP, mean blood pressure and HR in 1998 (r=0.40, 0.13, 0.11 and 0.14, respectively). The percentage change in BMI per year (DeltaBMI) was negatively correlated with log[leptin'96], even after adjustment for baseline BMI (r=-0.12, P=0.030). In men aged 30-63 years, log[leptin'96] was also positively correlated with BMI'98, SBP'98, DBP'98, FPG'98, TC'98, log[TG'98], LDL-C'98 and UA'98 (all P<0.05), and negatively correlated with HDL-C'98, DeltaBMI, DeltaFPG, DeltaTC and DeltaLDL-C. The relationship between log[leptin'96] and DeltaTC was significant, even after adjustment for initial BMI (r=-0.15, P=0.023). These findings therefore suggest that serum leptin levels are correlated with subsequent decreases in BMI and TC in Japanese men.


Subject(s)
Blood Pressure/physiology , Body Mass Index , Leptin/blood , Adolescent , Adult , Aging/blood , Cholesterol/blood , Follow-Up Studies , Heart Rate/physiology , Humans , Insulin/blood , Lipids/blood , Male , Middle Aged
8.
Ann Nucl Med ; 14(5): 379-81, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11108169

ABSTRACT

Thallium-201 (201Tl) scintigraphy is one of the imaging methods used in the detection of various tumors including brain metastasis. We evaluated a patient with meningeal carcinomatosis from breast cancer by using 201Tl single-photon emission computed tomography (SPECT). Meningeal spread of a tumor was noted on enhanced CT. SPECT revealed tumor localization in meningeal carcinomatosis. These results suggest that SPECT with 201Tl may be useful in detecting meningeal carcinomatosis from breast cancer.


Subject(s)
Breast Neoplasms/diagnostic imaging , Meningeal Neoplasms/diagnostic imaging , Meningeal Neoplasms/secondary , Thallium Radioisotopes , Breast Neoplasms/pathology , Fatal Outcome , Female , Humans , Middle Aged , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray Computed
9.
J Hypertens ; 18(11): 1557-61, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11081767

ABSTRACT

OBJECTIVE: This study was aimed to evaluate the determinants of elevated blood pressure (BP) in adolescents. DESIGN AND METHODS: We retrospectively evaluated the BP and anthropometric data in 419 Japanese students (268 males and 151 females) during high school and university. Their annual health records were analysed for BP, heart rate, height and body weight between the ages of 15 and 21 years. RESULTS: The number of hypertensive students did not vary significantly during the 6 years. Concerning changes in BP categories according to the modified JNCVI classification between the ages of 15 to 21 years, 150 males kept a normal BP (keeping normal BP group); 39 males developed high BP (developing high BP group); 37 males kept high BP (keeping high BP group); and 42 males became normal BP (becoming normal BP group). The majority of females (n = 144, 95.4%) were included in the keeping normal BP group. In male students, both the keeping and becoming normal BP groups, especially the latter, showed a significant decrease in heart rate over the 6 years, while the other two groups showed no change. The height and body weight of each of the four groups showed a significant increase, but the body mass index (BMI) of the males in the becoming normal BP group did not increase over the 6 years. Body weight and BMI at the age of 15 years in the male keeping normal BP group were significantly below that of the other three groups; this difference persisted at the age of 21 years. Furthermore, male university students who showed a BP above 'high-normal' at the age of 21 years exhibited a significantly higher BP, heart rate, body weight and BMI than did the normotensives, when they were high school students. Stepwise regression analysis of the data showed that the best predictors of BP at the age of 21 years were the initial high school BP and BMI levels and changes in BMI and heart rate during the 6-year period for male students. CONCLUSION: Results indicate that the BP and BMI during high school and the changes in BMI and heart rate from high school to university influenced the BP at the age of 21 years in male students. Data indicate that information on the prevention and management of hypertension including weight control should begin early, especially in male adolescents.


Subject(s)
Blood Pressure , Hypertension/diagnosis , Adolescent , Adult , Body Mass Index , Female , Follow-Up Studies , Heart Rate , Humans , Male , Obesity , Predictive Value of Tests , Retrospective Studies
11.
Hypertens Res ; 23(5): 421-6, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11016795

ABSTRACT

Numerous epidemiological studies have shown a close relationship between obesity and hypertension. However, there have been few reports on the relationship between changes in the body weight and blood pressure of lean to normal-weight young subjects. The purpose of this study was to investigate the effects of body weight control on blood pressure in lean to obese young Japanese individuals in a 3-year follow-up study. University students (3,558 males and 1,418 females, aged 18.6+/-0.8 in 1994) were classified into 4 groups according to the baseline body mass index (BMI), and were followed up for 3 years. Among male students, changes in body weight were significantly correlated with changes in blood pressure during the 3 years in all 4 BMI groups, and the correlation coefficient was larger in the group with higher baseline BMI. Positive correlations between changes in body weight and changes in heart rate were noted only in the obese and mildly-obese groups. Also in female students, positive correlations were observed between changes in body weight and changes in blood pressure in lean to obese groups. However, no correlations between changes in body weight and changes in heart rate were noted in any of the female groups. To summarize, close correlations were observed between changes in body weight and those in blood pressure during the 3 years in both male and female university students. These findings suggest the importance of body weight control not only in obese but also in normal to mildly-obese young subjects in reducing or preventing an increase in blood pressure. There could be, however, a gender difference in the effects of body weight change on heart rate.


Subject(s)
Blood Pressure , Body Weight , Hypertension/etiology , Obesity/complications , Adolescent , Adult , Age Factors , Body Mass Index , Female , Follow-Up Studies , Heart Rate , Humans , Life Style , Male , Sex Factors
12.
Oncogene ; 19(35): 4022-8, 2000 Aug 17.
Article in English | MEDLINE | ID: mdl-10962558

ABSTRACT

We have recently found a novel functional unit of cell-cell adhesion at cadherin-based adherens junctions, consisting of at least nectin, an immunoglobulin-like cell adhesion molecule, and afadin, an actin filament-binding protein which connects nectin to the actin cytoskeleton. Among the members of the nectin family, we have found here that nectin-2delta is tyrosine-phosphorylated in response to cell-cell adhesion. Expression of E-cadherin induced tyrosine phosphorylation of nectin-2delta, while disruption of cell-cell adhesion by an anti-E-cadherin antibody reduced the tyrosine phosphorylation of nectin-2delta. An inhibitor specific for Src family kinase or expression of Csk reduced tyrosine phosphorylation of nectin-2delta. In addition, Src kinase tyrosine phosphorylates the recombinant cytoplasmic region of nectin-2delta in vitro. The major tyrosine phosphorylation site of nectin-2delta was Tyr505 in the cytoplasmic region, because the mutant nectin-2delta, of which Tyr505 was replaced by Phe, showed a loss of tyrosine phosphorylation in vivo and in vitro. These results, together with our recent observations, indicate that the cadherin-catenin system and the nectin-afadin system are closely connected to each other. The cadherin-mediated cell-cell adhesion system may link to the activation of a Src family kinase, that is, at least in part, responsible for the tyrosine phosphorylation of the cytoplasmic region of nectin-2delta. Oncogene (2000) 19, 4022 - 4028.


Subject(s)
Cell Adhesion Molecules/metabolism , Cell Adhesion/physiology , Protein Processing, Post-Translational , Protein-Tyrosine Kinases/metabolism , Tight Junctions/physiology , src-Family Kinases/metabolism , Animals , COS Cells , Cadherins/physiology , Cell Line , Culture Media, Serum-Free , Epithelial Cells/metabolism , Female , Humans , Kinesins , Mammary Neoplasms, Experimental/pathology , Mice , Microfilament Proteins/metabolism , Myosins , Nectins , Phosphorylation , Phosphotyrosine/biosynthesis , Recombinant Fusion Proteins/metabolism , Transfection
13.
J Biol Chem ; 275(38): 29875-80, 2000 Sep 22.
Article in English | MEDLINE | ID: mdl-10896674

ABSTRACT

A neural plakophilin-related armadillo repeat protein (NPRAP)/delta-catenin interacts with one of Alzheimer disease-related gene products, presenilin 1. We have previously reported the interaction of NPRAP/delta-catenin with synaptic scaffolding molecule, which is involved in the assembly of synaptic components. NPRAP/delta-catenin also interacts with E-cadherin and beta-catenin and is implicated in the organization of cell-cell junctions. p0071, a ubiquitous isoform of NPRAP/delta-catenin, is localized at desmosomes in HeLa and A431 cells and at adherens junctions in Madin-Darby bovine kidney cells. We have identified here a novel protein interacting with NPRAP/delta-catenin and p0071 and named this protein plakophilin-related armadillo repeat protein-interacting PSD-95/Dlg-A/ZO-1 (PDZ) protein (PAPIN). PAPIN has six PDZ domains and binds to NPRAP/delta-catenin and p0071 via the second PDZ domain. PAPIN and p0071 are ubiquitously expressed in various tissues and are localized at cell-cell junctions in normal rat kidney cells and bronchial epithelial cells. PAPIN may be a scaffolding protein connecting components of epithelial junctions with p0071.


Subject(s)
Adaptor Proteins, Signal Transducing , Carrier Proteins/analysis , Carrier Proteins/genetics , Neoplasm Proteins , Nerve Tissue Proteins , Alzheimer Disease/metabolism , Amino Acid Sequence , Animals , Armadillo Domain Proteins , Carrier Proteins/metabolism , Catenins , Cattle , Cell Adhesion Molecules , Cloning, Molecular , Cytoskeletal Proteins/metabolism , Dogs , HeLa Cells , Humans , Membrane Proteins/metabolism , Molecular Sequence Data , Nerve Tissue Proteins/analysis , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Phosphoproteins , Plakophilins , Presenilin-1 , Rats , Sequence Alignment , Delta Catenin
14.
Hypertens Res ; 23(3): 227-32, 2000 May.
Article in English | MEDLINE | ID: mdl-10821131

ABSTRACT

The effects of belonging to sports clubs on male high school students was evaluated. The relationships between the type and extent of school-based exercise were examined in conjunction with percent body fat, blood pressure (BP), and other key metabolic parameters. A total of 264 male Japanese high school students (age range: 17-18 years old) were studied. Percent body fat was measured and blood was collected in the fasting state during a routine health check. Subjects were divided into two groups. The exercise (E) group (n=150) included students who had belonged to a sports club during the past 2 years. The non-exercise (NE) group (n=114) included students who did not belong to a sports club during the past 2 years. The body mass index was significantly greater in group E (21.7 +/- 2.3 (SD) kg/m2) than in group NE (20.7 +/- 2.6 kg/m2, p < 0.01). However, the percent body fat in group E (13.6 +/- 3.4%) was significantly lower than that in group NE (14.9 +/- 3.8%, p < 0.01). The diastolic BP and heart rate in group E (64 +/- 7 mmHg, 70 +/- 11/min) were significantly lower in group E than in group NE (66 +/- 8 mmHg, p < 0.05; 76 +/- 14/min, p < 0.01). The serum triglyceride level was significantly lower, and the HDL cholesterol level was higher in group E than in group NE. The homeostasis model assessment (HOMA) index, used as an index of insulin resistance, was similar in the two groups. However, the level of the HOMA index was significantly lower among the 62 subjects in group E who preferred highly dynamic exercise (1.50 +/- 0.46) than it was among those in group NE (1.66 +/- 0.49, p < 0.05). Results indicate that belonging to sports clubs influences the BP and lipid profiles of adolescent males, as well as their percent body fat. In view of the reduction of cardiovascular risk factors, it is recommended that even young males practice regular exercise, especially aerobic exercise.


Subject(s)
Blood Pressure , Cardiovascular Diseases/epidemiology , Sports , Adolescent , Body Mass Index , Cardiovascular Diseases/prevention & control , Cholesterol, HDL/blood , Exercise , Humans , Insulin Resistance , Male , Obesity/epidemiology , Obesity/prevention & control , Risk Factors , Schools , Triglycerides/blood
15.
Genes Cells ; 5(3): 203-10, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10759891

ABSTRACT

BACKGROUND: Synapse-associated protein (SAP) 90/Postsynaptic density (PSD)-95-associated protein (SAPAP) (also called Guanylate kinase-associated protein/hDLG-associated protein) interacts with the guanylate kinase domains of PSD-95 and synaptic scaffolding molecule (S-SCAM) via the middle region containing 5 repeats of 14 amino acids. SAPAP also binds the recently identified proteins, nArgBP2 and synamon (also called Shank 1a), via the proline-rich region and the C-terminus, respectively. SAPAP is highly enriched in the Triton X-100-insoluble PSD fraction, and recruits PSD-95 into the Triton X-100-insoluble fraction in transfected cells. We have further characterized here the Triton X-100-insolubility of SAPAP and tried to identify the Triton X-100-insoluble structures which SAPAP interacts with. RESULTS: N-Methyl-D-aspartate receptors were recruited into the Triton X-100-insoluble fraction with PSD-95 by SAPAP. The N-terminal region of SAPAP was Triton X-100-insoluble, whereas the middle and C-terminal regions were Triton X-100-soluble. We identified proteins interacting with 35S-methionine-labelled SAPAP in the overlay assay, determined their amino acid sequences, and found them to be neurofilaments. SAPAP interacted with neurofilaments via the N-terminal region, was co-immunoprecipitated with neurofilaments from the rat brain, and co-localized with neurofilaments in transfected cells. CONCLUSION: SAPAP associates with neurofilaments via the N-terminal region and may link various components of the PSD to neurofilaments.


Subject(s)
Actin Cytoskeleton/metabolism , Nerve Tissue Proteins , Synapses , Animals , CHO Cells , Cricetinae , Nerve Tissue Proteins/metabolism , Neurofilament Proteins/metabolism , Rats , SAP90-PSD95 Associated Proteins , Transfection
16.
J Biol Chem ; 275(4): 2966-72, 2000 Jan 28.
Article in English | MEDLINE | ID: mdl-10644767

ABSTRACT

The synaptic scaffolding molecule (S-SCAM) has been identified as a protein interacting with SAP90/PSD-95-associated protein (SAPAP) (also called guanylate kinase-associated protein/hDLG-associated protein). S-SCAM has six PDZ (we have numbered them PDZ-0 to -5), two WW, and one guanylate kinase (GK) domains and interacts with N-methyl-D-aspartate (NMDA) receptor via PDZ-5 and SAPAP via the GK domain. We have identified here shorter isoforms of S-SCAM that start at the 164th or 224th methionine, and we renamed the original one, S-SCAMalpha, the middle one, S-SCAMbeta, and the shortest one, S-SCAM-gamma. S-SCAMbeta and -gamma have five PDZ (PDZ-1 to -5), two WW, and one GK domains. S-SCAMalpha interacted with S-SCAMbeta and -gamma through the region containing PDZ-4 and -5. The region containing both of PDZ-4 and -5 is sufficient for the clustering of NMDA receptors and forms a dimer in gel filtration, suggesting that S-SCAM forms multimers via the interaction between the C-terminal PDZ domains and assembles NMDA receptors into clusters. S-SCAMbeta and -gamma also interacted with SAPAP, suggesting that the N-terminal region of the GK domain is not necessary for the interaction. Finally, we have identified the interaction of the PDZ domains of S-SCAM with the GK domain of PSD-95/SAP90. S-SCAM, PSD-95/SAP90, and SAPAP are colocalized at least in some part in brain. Therefore, S-SCAM, PSD-95/SAP90, and SAPAP may form a complex in vivo.


Subject(s)
Carrier Proteins/metabolism , Nerve Tissue Proteins/metabolism , Protein Isoforms/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Adaptor Proteins, Signal Transducing , Amino Acid Sequence , Animals , Base Sequence , Biopolymers , CHO Cells , COS Cells , Carrier Proteins/chemistry , Cerebellum/metabolism , Chromatography, Gel , Cricetinae , DNA Primers , Guanylate Kinases , Microscopy, Fluorescence , Molecular Sequence Data , Nerve Tissue Proteins/chemistry , Protein Binding , Protein Isoforms/chemistry , Rats , Retina/metabolism , SAP90-PSD95 Associated Proteins , Sequence Homology, Amino Acid
17.
Endocr Res ; 26(4): 791-5, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11196456

ABSTRACT

The aim of the present study was to assess the long-term results of adrenalectomy and to evaluate potential risk factors for the persistence or recurrence of hypertension. Forty-five patients with Cushing's syndrome caused by benign cortisol-producing adrenocortical adenomas were evaluated before and for a period of 1 year after surgical cure. When the patients were classified into two groups according to whether their preoperative BP was more (HBP group) or less (NBP group) than 140/90 mmHg, the BP level was found to be continuously higher in the HBP group than in the NBP group during the year after surgery. This finding suggests that the preoperative BP level in Cushing's syndrome may be a determinant factor for persistent hypertension after surgery (P<0.05). In addition, a correlation was found between postoperative BP level and duration of hypertension (P<0.05), but no relationships were found between postoperative BP levels and other factors, including age, BMI, tumor size, serum cortisol, aldosterone, potassium, total cholesterol, or glucose levels. The above findings indicate that intensive control of preoperative BP to maintain it below 140/90 mmHg with antihypertensive medication is a very important means of improving prognosis for postoperative BP. Immediate diagnosis and surgical treatment to reduce the duration of hypertension are also crucial for the long-term BP prognosis.


Subject(s)
Adrenalectomy , Cushing Syndrome/surgery , Hypertension/etiology , Postoperative Complications/etiology , Adult , Blood Pressure , Cushing Syndrome/physiopathology , Female , Humans , Hypertension/physiopathology , Hypertension/prevention & control , Male , Risk Factors , Time Factors
18.
Biochem Biophys Res Commun ; 270(2): 538-42, 2000 Apr 13.
Article in English | MEDLINE | ID: mdl-10753660

ABSTRACT

Membrane-associated guanylate kinase-interacting protein (MAGUIN)-1 was identified as a protein interacting with synaptic scaffolding molecule (S-SCAM) and postsynaptic density (PSD)-95/synapse-associated protein (SAP)90. MAGUIN-1 has a chimerical molecular structure composed of one sterile alpha motif, one PSD-95/Dlg-A/ZO-1 (PDZ), and one pleckstrin homology (PH) domain, and interacts with the PDZ domains of S-SCAM and PSD-95/SAP90 via its carboxyl-terminal PDZ-binding motif. MAGUIN-1 is considered as a mammalian homologue of Drosophila CNK, which is a Raf-interacting protein implicated in the regulation of eye development. Here we have tested whether MAGUIN-1 interacts directly with Raf-1. MAGUIN-1 and Raf-1 were coimmunoprecipitated from rat brain. MAGUIN-1 binds to the kinase domain of Raf-1, and Raf-1 binds to the middle region of MAGUIN-1 containing the PH domain. However, in contrast to the dominant active mutant of Ki-Ras, which interacts with Raf-1, recruits it to the plasma membrane from the cytosol, and activates it, MAGUIN-1 neither activates Raf-1 nor recruits it to the plasma membrane. MAGUIN-1 may link Raf-1 to components of synapses assembled by PSD-95/SAP90 and S-SCAM.


Subject(s)
Adaptor Proteins, Signal Transducing , Carrier Proteins/metabolism , Nerve Tissue Proteins/metabolism , Proto-Oncogene Proteins c-raf/metabolism , Amino Acid Sequence , Animals , CHO Cells , COS Cells , Cricetinae , Enzyme Activation , Glutathione Transferase/metabolism , In Vitro Techniques , Mitogen-Activated Protein Kinases/metabolism , Molecular Sequence Data , Protein Binding , Rats
19.
J Biol Chem ; 274(43): 30914-8, 1999 Oct 22.
Article in English | MEDLINE | ID: mdl-10521485

ABSTRACT

Postsynaptic density (PSD)-95/synapse-associated protein (SAP) 90 and synaptic scaffolding molecule (S-SCAM) are synaptic membrane-associated guanylate kinases. Both the proteins interact with SAP90/PSD-95-associated protein (SAPAP) (also called guanylate kinase-associated protein/Dlg-associated protein). SAPAP is a protein highly enriched in the PSD fraction and may link PSD-95/SAP90 and S-SCAM to Triton X-100-insoluble structures. We found here a novel SAPAP-interacting protein, which was specifically expressed in neural tissue and was present in the postsynaptic density fraction in brain. This protein had a sorbin homology domain in the N terminus, a zinc finger motif in the middle region, and three src homology (SH) 3 domains in the C terminus and was homologous to the ponsin/ArgBP2/vinexin family proteins. We named this protein nArgBP2 because it was the most homologous to ArgBP2. nArgBP2 is a neural member of a growing family of SH3-containing proteins. nArgBP2 bound to the proline-rich region of SAPAP via its third SH3 domain and was coimmunoprecipitated with SAPAP from the extract of rat brain. Furthermore, nArgBP2 was colocalized with SAPAP at synapses in cerebellum. nArgBP2 bound to not only SAPAP but also vinculin and l-afadin, known to bind to ponsin and vinexin. nArgBP2 may be implicated in the protein network around SAPAP in the PSD.


Subject(s)
Adaptor Proteins, Signal Transducing , Brain/metabolism , Nerve Tissue Proteins/metabolism , Amino Acid Sequence , Animals , Binding Sites , Cloning, Molecular , Disks Large Homolog 4 Protein , Gene Expression , Homeodomain Proteins/metabolism , Intracellular Signaling Peptides and Proteins , Membrane Proteins , Microfilament Proteins/metabolism , Molecular Sequence Data , Muscle Proteins/metabolism , Organ Specificity , Rats , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , SAP90-PSD95 Associated Proteins , Zinc Fingers , src Homology Domains
20.
Hypertens Res ; 22(3): 169-72, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10515438

ABSTRACT

This study was designed to examine the relationships between birth weight or current body weight and blood pressure (BP) or cholesterol in 178 Japanese high school students (98 male, 80 female, age 15-16 yr). All subjects were born after a full-term pregnancy (gestational age > or = 38 wk) with a birth weight > or = 2,500 g; these data were obtained from routine obstetrical records. At a health check-up, nurses used an automatic device to perform two consecutive BP measurements with each subject in a sitting position after resting for at least 5 min. Serum total and high-density lipoprotein (HDL) cholesterol levels were measured. Birth weight was not related to BP, but was inversely related to serum total cholesterol in both males (r= -0.241, p < 0.05) and females (r= -0.351, p < 0.01). Current body weight was significantly related to systolic BP (r=0.369, p<0.01), diastolic BP (r=0.216, p<0.05), and HDL cholesterol level (r= -0.224, p < 0.05) in males, but not in females. Although no relationship was demonstrated between birth weight and BP level in young Japanese students without intrauterine growth retardation, an inverse relationship between birth weight and serum total cholesterol level was found. There was a gender difference in the relationship between current body weight and either BP or HDL cholesterol in these subjects.


Subject(s)
Birth Weight , Blood Pressure , Body Weight , Cholesterol/blood , Adolescent , Female , Humans , Japan , Male , Pregnancy
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