PubMed Health⌕ Search

Biomedical subjects

M Sunamoto

Publications and source records attributed to M Sunamoto.

12 recordsLinked to original sources
PubMed2000

Autocrine action and its underlying mechanism of nitric oxide on intracellular Ca2+ homeostasis in vascular endothelial cells.

The rise in cytosolic Ca(2+) concentration (Ca(2+)(i)) in vascular endothelial cells (ECs) activates the production and release of nitric oxide (NO). NO modifies Ca(2+)(i) homeostasis in many types of nonendothelial cells. However, its effect on endothelial Ca(2+)(i) homeostasis at basal and excited states remains unclear. In the present study, to elucidate the effect of NO on basal Ca(2+)(i), inositol 1,4,5-trisphosphate-induced Ca(2+)(i) release (IICR) was blocked by expressing an antisense against type-1 inositol 1,4,5-trisphosphate receptors or by microinjecting heparin to individual ECs, and the effects of NO that was released by and diffused from adjacent IICR-intact ECs were recorded. After ATP or bradykinin stimulation, IICR-inhibited ECs showed a marked reduction of basal Ca(2+)(i), which was abolished by N(G)-monomethyl-l-arginine monoacetate pretreatment. The reduction disappeared in sparsely seeded ECs. Exogenous NO gas mimicked the effect of ATP or bradykinin to reduce basal Ca(2+)(i). Blocking plasma membrane Ca(2+)-ATPase (PMCA), but not Na(+)-Ca(2+) exchange or sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase, suppressed the reduction, indicating that the reduction resulted from a NO-dependent potentiation of PMCA. To elucidate the effect of NO on elevated Ca(2+)(i), ATP-, bradykinin-, or thapsigargin-evoked Ca(2+)(i) response in the presence and absence of NO production was compared in adjacent IICR-intact ECs. NO was found to potentiate PMCA, which, in turn, greatly attenuated agonist-evoked Ca(2+)(i) elevation. NO also potentiated Ca(2+) influx, which markedly increased the sustained phase of Ca(2+)(i) elevation and possibly NO production. NO did not affect other Ca(2+)(i)-elevating and Ca(2+)(i)-sequestrating components. Thus, NO-dependent potentiation of PMCA is crucial for Ca(2+)(i) homeostasis over a wide Ca(2+)(i) range.

Adenosine Triphosphate↗
PubMed1998

A multifunctional transcription factor (A1p145) regulates the smooth muscle phenotype in mesangial cells.

A1p145, a novel DNA binding protein for type IV collagen gene (COL4), has multiple functions including DNA replication factor C and DNA binding for several other genes. To elucidate the mechanisms underlying the differentiation process of mesangial cells (MCs), we investigated the effects of A1p145 on rat MCs. Cells in the early passages showed a smooth muscle-like phenotype such as low cell turnover, high levels of expression for COL4, and smooth muscle alpha-actin (SMA). Cells in the late passages lost their phenotype. The amount of binding activity to COL4 promoter was inversely correlated with the level of COL4 mRNA. Introduction of antisense for A1p145 into late passage cells enhanced the levels of mRNA for COL4 and SMA. The levels of proliferating cell nuclear antigen mRNA were also suppressed. These results suggest that A1p145 is a negative transcription factor for COL4 and may be a phenotypic modulator.

Actins↗
PubMed1998

Expression of heat shock protein 47 is increased in remnant kidney and correlates with disease progression.

Glomerulosclerosis is characterized by accumulation of the mesangial extracellular matrix, including type I and V collagen. The processing for the collagens in the glomeruli may play a critical role for development of glomerulosclerosis. We examined the expression of heat shock protein 47 (HSP47), a collagen-binding molecular chaperone in the progressive glomerulosclerosis model. Subtotally nephrectomized rats, unlike sham-operated rats, developed focal and segmental glomerulosclerosis. Immunological staining demonstrated an increased expression of HSP47 which paralleled the expression of type I and IV collagen in the glomeruli of the nephrectomized rats as the glomerulosclerosis developed. The mRNA levels encoding type I and type IV collagen and HSP47 were increased 3.4 fold, 3.6 fold and 2.8 fold, respectively, at week 7 after nephrectomy. By in situ hybridization, the expression of HSP47 mRNA was determined to be localized to the glomeruli with segmental sclerosis. These results suggest that HSP47 may play a central role in the process of extracellular matrix accumulation during the development of glomerulosclerosis.

Animals↗
PubMed1998

Antisense oligonucleotides against collagen-binding stress protein HSP47 suppress collagen accumulation in experimental glomerulonephritis.

Heat shock protein 47 (HSP47) is a collagen-specific molecular chaperone that has been shown to play a major role during the biosynthesis and secretion of procollagen molecules. The expression of HSP47 has been reported to increase in parallel with the expression of collagens during the progression of various fibrosis models. However, it remains unclear whether an inhibition of HSP47 overexpression would suppress collagen accumulation and thus reduce the progression of fibrotic diseases. In this study, we attempted to attenuate glomerular collagen accumulation by inhibiting the overexpression of HSP47 with antisense oligodeoxynucleotides in an experimental glomerulonephritis model induced by anti-Thy-1 antibodies. The administration of antisense oligodeoxynucleotides against HSP47 at the induction of the glomerular disease markedly suppressed the increased production of collagens and attenuated the histologic manifestations of the disease. These results provide direct evidence of a pivotal role for HSP47 in the pathogenesis of glomerulonephritis.

Animals↗
PubMed1997

A novel transcription factor is correlated with both glomerular proliferation and sclerosis in the rat renal ablation model.

Glomerular accumulation of the extracellular matrix (ECM) with subsequent sclerosis is a common finding in most progressive renal diseases. Recently MSW (Mouse South Western) protein was cloned by its ability to bind the bidirectional promoter of the collagen IV genes. This protein was also reported as the large subunit of the DNA replication complex A1, as well as the promoter binding protein of corticotropin-releasing hormone and the angiotensinogen gene. To investigate the mechanism of accumulation of the ECM as it relates to glomerular cellular events, the expression of MSW protein was studied in the remnant kidney model. Progressive expression of MSW protein was found in the glomerular sclerotic lesion at week 4 and at later time points after renal ablation. The expression of proliferating cell nuclear antigen (PCNA) and type IV collagen was also correlated with the expression of MSW protein by immunofluorescence. RNA dot blot analysis also showed that the expression of MSW mRNA was increased at week 7 in association with the augmented expression of type IV collagen. These results, taken together, suggest that MSW protein plays an important role in the regulation of type IV collagen gene expression in vivo and may contribute to glomerular cell proliferation and the development of glomerulosclerosis.

Animals↗
PubMed1996

beta-Amyloid protein-dependent nitric oxide production from microglial cells and neurotoxicity.

beta-Amyloid protein (A beta) is the major component of the senile plaques in Alzheimer's disease (AD), and microglial cells have been shown to be closely associated with these plaques. However, the roles of A beta and microglial cells in pathogenesis of AD remain unclear. Incubation of rat microglial cells with A beta(1-40) caused a significant increase in nitrite, a stable metabolite of nitric oxide (NO), in culture media, while there was no detectable increase in nitrite in astrocyte-rich glial cells or cortical neurons after incubation with A beta(1-40). Nitrite production by microglial cells was also induced by A beta(1-42), but not A beta(25-35). An inhibitor of NO synthase, NG-monomethyl-L-arginine (NMMA), as well as dexamethasone and actinomycin D, dose-dependently inhibited this nitrite production. Among the various cytokines investigated such as interleukin-1, interleukin-6, tumor necrosis factor-alpha and interferon-gamma (IFN-gamma), only IFN-gamma markedly enhanced A beta-dependent nitrite production. Cultured cortical neurons were injured by microglial cells stimulated with A beta in a dose-dependent manner in the presence of IFN-gamma. Neurotoxicity caused by the A beta plus IFN-gamma-stimulated microglial cells was significantly attenuated by NMMA. Thus, although further investigations into the effect of A beta on human microglial cells are needed, it is likely that A beta-induced NO production by microglial cells is one mechanism of the neuronal death in AD.

Amyloid beta-Peptides↗
PubMed1995

Immunohistochemical expression of inducible nitric oxide synthase (iNOS) in reversible endotoxic shock studied by a novel monoclonal antibody against rat iNOS.

An antirat monoclonal antibody (mAb) against inducible nitric oxide synthase (iNOS), ANOS11, was used for immunohistochemistry to examine the expression of iNOS in various organs and tissues of adult rats in experimental endotoxic shock induced by lipopolysaccharide (LPS) injection. The phenotype of iNOS-expressed cells was also examined immunohistochemically using various mAbs. In control rats, very few cells were positive for ANOS11 except in the thymus. After intravenous injection of LPS, the number of iNOS-positive cells increased rapidly in almost all organs, except the thymus and brain, peaked 6 h after the injection, and decreased slowly. Of the numerous inflammatory cells that infiltrated the lungs, liver, and spleen after LPS injection, many were positive for ANOS11. Besides inflammatory cells, hepatocytes and endothelial cells of the aorta were also positive for ANOS11 but only around 6 h after injection. The cellular composition of iNOS-positive infiltrated cells changed along with the progression of endotoxic shock. At 4 to 6 h after injection, most iNOS-positive cells were considered polymorphonuclear leukocytes judging by their positive reactivity to OX42 and their nuclear morphology. The population of iNOS-positive macrophages positive for ED1 or ED2 increased with time. After 24 h, many iNOS-positive macrophages were found around the focal necrosis in the liver and spleen. These results indicate that the expression of iNOS in neutrophils, endothelial cells, and hepatocytes precedes that of macrophages in experimental endotoxic shock. The expression of iNOS in various cells and organs is closely associated with the progress and pathological changes of endotoxic shock.

Amino Acid Oxidoreductases↗
PubMed1993

Stabilization of inducible nitric oxide synthase by monoclonal antibodies.

We have produced 14 monoclonal antibodies to inducible nitric oxide synthase purified from rat peritoneal cytotoxic activated macrophages. None of the antibodies showed neutralizing activity, but some of them enhanced the enzyme activity through stabilization of the enzyme.

Amino Acid Oxidoreductases↗
PubMed1993

[Pharmaceutical characterization of silicone elastomer implant system containing chlormadinone acetate for prevention of estrus in bitches].

We developed a new subdermal silicone elastomer implants containing chlormadinone acetate (CMA), which was effective for prevention of estrus in bitches. The implants gave a continuous CMA release over a year. The CMA release from the implants was dependent on the CMA loading level and surface area of the implants. The CMA release patterns both in vitro and in vivo system fitted well with the Higuchi square root low. The dissolution test using organic solvents was found to be useful for the brief estimation of CMA release from the implants.

Animals↗
PubMed1993

[Effectiveness of dapsone on refractory immune thrombocytopenia in a patient with systemic lupus erythematosus associated with sarcoidosis].

A 57-year-old man was admitted with massive nasal bleeding and blurred vision in January, 1991. Laboratory examination showed a prominent decrease of platelet number (1,000/microliters) and a marked elevation of PAIgG (4,025 ng/10(7) cells). Serological test revealed positive antinuclear factor, low concentration of C3 and C4, high level of immune complex and polyclonal hypergammaglobulinemia. The patient had uveitis and bilateral hilar lymphadenopathy with a high level of serum lysozyme and negative PPD skin test. The diagnosis of SLE complicated with thrombocytopenia and sarcoidosis was made. In spite of the various trials of treatment, such as oral prednisolone (PSL), methyl-PSL pulse therapy, plasma exchange, high-dose intravenous gammaglobulin, cyclophosphamide, azathioprine, vincristine, colchicine, cyclosporine-A, mizoribine, danazol, ascorbic acid and interferon alpha 2b, the platelet number could not be raised enough to keep more than 10,000/microliters, though the level of PAIgG decreased to 200 ng/10(7) cells. Finally, the administration of 75 mg/day of dapsone brought about a significant rise in platelet number within 2 weeks. The maximum number of 6.2 x 10(4)/microliters was obtained after 2 months. Then the patient stopped himself to take the drug, but the platelet number remained around 4-5 x 10(4)/microliters. Same dose of the drug was again prescribed to confirm the effect of dapsone. The platelet number increased to 7.9 x 10(4)/microliters in 2 weeks, and gradually returned to 5 x 10(4)/microliters after cessation of the drug. Thus being certainly effective against thrombocytopenia, dapsone should be considered as one of the therapeutic choice for refractory autoimmune thrombocytopenia.

Autoimmune Diseases↗
PubMed1986

[Effects of misoprostol, (+/-)-methyl (11 alpha, 13E)-11, 16-dihydroxy-16-methyl-9-oxoprost-13-en-l-oate, on various gastric and duodenal lesions in rats].

Male Sprague-Dawley rats (230-280 g), either fasted for 15-24 hr or non-fasted prior to experiments, were used. Misoprostol (3-100 micrograms/kg, p.o.) dose-dependently inhibited the development of 150 mM HCl X aspirin (100 mg/kg)-, 150 mM HCl X 60% ethanol-, and aspirin (150 mg/kg)-induced gastric lesions. Misoprostol (30, 100 micrograms/kg, p.o.), given twice daily for 4 days, significantly inhibited prednisolone (50 mg/kg given once daily for 4 days)-induced gastric lesions. Misoprostol (30 or 2 X 300 micrograms/kg, p.o.) also significantly inhibited water-immersion stress (21 degrees C, 10 hr)-induced gastric lesions or mepirizole (200 mg/kg)-induced duodenal lesions, respectively. In contrast, misoprostol (30-300 micrograms/kg, p.o.) had no effects on indomethacin (25 mg/kg)- and mepirizole (200 mg/kg)-induced gastric lesions. Misoprostol (30 micrograms/kg, p.o.) had no effect on gastric secretion in pylorus-ligated preparations (4 hr), but it (100 or 300 micrograms/kg, p.o.) significantly increased the volume and pepsin output. Gastric motility, either normal or enhanced with indomethacin (25 mg/kg), was inhibited by misoprostol (30 or 300 micrograms/kg, p.o.). Misoprostol (30 micrograms/kg, i.d.) significantly stimulated duodenal HCO3- secretion. Mechanisms by which misoprostol inhibits various gastric lesions remain unknown. However, the stimulatory activity on duodenal HCO3- secretion appears to be involved in the preventive effect of misoprostol on the development of duodenal lesions. The effects of cimetidine and 16,16-dimethyl PGE2 were also studied and compared with those of misoprostol.

Alprostadil↗