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Biomedical subjects

M Noda

Publications and source records attributed to M Noda.

At least 379 records · Page 21Linked to original sources
PubMed1994

Induction of apoptosis by the mouse Nedd2 gene, which encodes a protein similar to the product of the Caenorhabditis elegans cell death gene ced-3 and the mammalian IL-1 beta-converting enzyme.

By subtraction cloning we previously identified a set of mouse genes (named Nedd1 through Nedd10) with developmentally down-regulated expression in brain. We now show that one such gene, Nedd2, encodes a protein similar to the mammalian interleukin-1 beta-converting enzyme (ICE) and the product of the Caenorhabditis elegans cell death gene ced-3 (CED-3). Both ICE and CED-3 are known to encode putative cysteine proteases and induce apoptosis when overexpressed in cultured cells. Overexpression of Nedd2 in cultured fibroblast and neuroblastoma cells also resulted in cell death by apoptosis, which was suppressed by the expression of the human bcl-2 gene, indicating that Nedd2 is functionally similar to the ced-3 gene in C. elegans. We also show that during embryonic development, Nedd2 is highly expressed in several types of mouse tissue undergoing high rates of programmed cell death such as central nervous system and kidney. Our data suggest that Nedd2 is an important component of the mammalian programmed cell death machinery.

Amino Acid Sequence↗
PubMed1994

Synergistic stimulation of parathyroid hormone-related peptide gene expression by mechanical stretch and angiotensin II in rat aortic smooth muscle cells.

Repetitive cyclic stretch (60 cycles/min) of rat aortic smooth muscle cells dramatically enhances the effect of angiotensin II (AII) on mRNA expression of the vasorelaxant, parathyroid hormone-related peptide (PTHrP). Thus, combined stimulation of rat aortic smooth muscle cells by cyclic stretch and low concentrations of AII, but not either alone, induces a synergistic, marked increase in the PTHrP mRNA level, in a manner dependent on the strength of stretch. This response is accompanied by a synergistic increase in secretion of PTHrP from smooth muscle cells. Removal of extracellular Ca2+ or addition of Ca2+ channel blockers, including Gd3+ and nitrendipine, does not considerably reduce the combined effects of stretch and AII, indicating that this response is not dependent on stretch-induced Ca2+ influx across the plasma membrane. The combined effect of stretch and AII on PTHrP mRNA expression is strongly attenuated by the protein kinase C (PKC) inhibitor staurosporine or by down-regulation of PKC, suggesting that PKC plays an important role in the synergistic response. However, stretch neither elicits activation of phospholipase C or PKC by itself, nor does it enhance AII-induced activation of these enzymes. These results indicate that in vascular smooth muscle cells mechanical stretch acts together with the vasoconstrictor AII to regulate the expression of the vasodilator PTHrP and suggest the role of PTHrP as a local modulator of myogenic tone.

Alkaloids↗
PubMed1994

Activation of inward current associated with M-potassium current inhibition in m1-muscarinic receptor-transformed NG108-15 cells by KST-5452, a novel cognition enhancer.

The electrophysiological effects of KST-5452 [3-(m-phenoxybenzylidene)-quinuclidine], an M1 muscarinic acetylcholine receptor (muscarinic AChR) binding compound, were studied in NG108-15 neuroblastoma x glioma hybrid cells transfected with m1 muscarinic AChR cDNA. Application of KST-5452 to m1-transformed NGPM1-27 cells elicited a sustained inward current associated with decreased conductance and reduced M-current relaxations at a holding potential of -20 mV. The KST-5452-induced responses were blocked by pirenzepine, suggesting that KST-5452 acts as a potent excitant via M1 muscarinic AChRs in brain neurons.

Acetylcholine↗
PubMed1994

Molecular cloning and biological activity of a novel developmentally regulated gene encoding a protein with beta-transducin-like structure.

In the developing mammalian central nervous system, neural precursor cells show a tightly regulated inverse relationship between cell proliferation and differentiation. The molecular mechanisms which control the inter-relationship between these two events are poorly understood. To approach this problem, we previously identified several novel genes which are most prominently expressed in the early embryonic brain. Further cloning and sequencing of one such gene, Nedd1, revealed that it can encode a protein with a M(r) of 71,000, the amino-terminal half of which shares significant structural similarity with the beta-subunit of heterotrimeric GTP-binding proteins. Nedd1 mRNA is strongly expressed in early embryonic brain, but it can be detected at low levels in a number of adult tissues as well as cell lines and is up-regulated in an embryonal carcinoma cell line upon retinoic acid-induced differentiation. Ectopic expression of Nedd1 gene by means of eukaryotic vectors in various cell lines resulted in varying degrees of growth suppression. The strongest effects were evident in differentiation-competent neuroblastoma-derived cell lines. Our results suggest that the Nedd1 gene may play a role in the differentiation-coupled growth arrest in neuronal cells.

Amino Acid Sequence↗
PubMed1994

Newly identified genes involved in the signal transduction of Escherichia coli K-12.

We cloned and sequenced two Escherichia coli genes which are members of a family of an environmentally responsive two-component system. The nucleotide (nt) and deduced amino-acid sequences of these two genes were found to be homologous to those of the Bordetella pertussis bvgA and bvgS genes. They were mapped at 51 min (clones 6B9 to 7G9 of the Kohara miniset library of the E. coli chromosome). Both proteins, deduced from their nt sequences, were identified in the coupled in vitro transcription-translation system; their molecular masses were consistent with BvgA and BvgS (23 and 135 kDa, respectively). Furthermore, when these genes were expressed on a multicopy plasmid in an envZ deletion strain, ompC expression was induced. This expression was found to be regulated by low temperature, MgSO4 and nicotinic acid, factors known to control the virulence of B. pertussis via BvgA and BvgS. These results indicate that the newly cloned genes were structurally and functionally similar to bvgA and bvgS, and we designated these genes evgA and evgS.

Amino Acid Sequence↗
PubMed1994

Effect of an angiotensin II receptor antagonist, CV-11974, and its prodrug, TCV-116, on production of aldosterone.

In dispersed rabbit adrenocortical glomerulosa cells, a non-peptide angiotensin II (AT1) receptor antagonist, CV-11974 (10(-10)-10(-5) M), competitively inhibited angiotensin II- or angiotensin III-stimulated aldosterone production, whereas PD123177, an angiotensin AT2 receptor antagonist, did not. CV-11974 inhibited aldosterone production induced by 4 mM K+ but not by 12 mM K+. CV-11974 had no effect on adrenocorticotropic hormone-stimulated aldosterone or corticosterone production, but inhibited angiotensin II-stimulated corticosterone production. In the rat, TCV-116, the prodrug of CV-11974, (0.1 and 1 mg/kg, p.o.) markedly reduced the elevation of both plasma aldosterone concentration and blood pressure induced by i.v. infusion of angiotensin II. In spontaneously hypertensive rats, TCV-116 at daily p.o. doses of 0.1, 1 and 10 mg/kg for 2 weeks caused a dose-dependent reduction of blood pressure and plasma aldosterone concentration without affecting plasma corticosterone. Thus, TCV-116 inhibited the induction of aldosterone production by not only exogenous but also endogenous angiotensin II.

Administration, Oral↗
PubMed1994

Dexamethasone enhancement of betaglycan (TGF-beta type III receptor) gene expression in osteoblast-like cells.

Betaglycan (type III transforming growth factor-beta (TGF-beta) receptor) is a cell surface heparan/chondroitin sulfate proteoglycan that binds TGF-beta via its core protein and is abundantly expressed in osteoblastic cells. A previous report (Centrella et al., Mol. Cell. Biol. 11, 4490-4496, 1991) showed post-translational enhancement by glucocorticoid of TGF-beta binding to betaglycan. Upon the availability of the betaglycan cDNA, we investigated the effects of a glucocorticoid analogue, dexamethasone, on the regulation of betaglycan expression in osteoblast-like cells. Betaglycan mRNA was expressed as an approximately 6-kb band in MC3T3-E1 cells. The betaglycan mRNA level was enhanced severalfold by dexamethasone in these cells. The effect of dexamethasone on the betaglycan mRNA level was observed within 9 h and was sustained at least up to 48 h. The dexamethasone effect was dose-dependent, with a saturation concentration at 10(-7) M. Among the steroid hormones examined, dexamethasone exhibited the most potent effect on betaglycan mRNA expression, while retinoic acid also enhanced it moderately. Dexamethasone enhancement of betaglycan mRNA expression was blocked by actinomycin D, but it was not blocked by cycloheximide. Cross-linking experiments showed that dexamethasone treatment increased the binding of radiolabeled TGF-beta 1 to betaglycan, but did not affect binding to the type II receptor. A similar dexamethasone enhancement of betaglycan mRNA expression was also observed in a preosteoblast-like cell line, RCT1. These results suggest that dexamethasone enhances betaglycan expression at least in part via transcriptional events in osteoblasts and this would be one of the target points of glucocorticoid regulation of bone metabolism.

Animals↗
PubMed1994

Hyperproinsulinemia in Japan.

Four families with hyperproinsulinemia found in Japan were described. The details of the first case, who was investigated by Kanazawa et al., were reported and the similarity of the first case to the following cases was shown. Arginine 65 of the proinsulin molecule might be a hot spot of the insulin gene. A possible abnormality of insulin release in affected individuals was disclosed by investigation of the family members of the first case.

Arginine↗
PubMed1994

Identification of a DNA sequence involved in osteoblast-specific gene expression via interaction with helix-loop-helix (HLH)-type transcription factors.

To elucidate regulatory mechanism(s) underlying differentiation of osteoblasts, we examined involvement of helix-loop-helix (HLH)-type transcription factors in osteoblast-specific expression of a phenotypic marker gene which encodes osteocalcin, a major noncollagenous bone matrix protein, exclusively expressed in osteoblasts. Overexpression of a dominant negative HLH protein, Id-1, decreased the activity of the 1.1-kb osteocalcin gene promoter cotransfected into rat osteoblastic osteosarcoma ROS17/2.8 cells. Analysis of deletion mutants revealed that a 264-bp fragment of osteocalcin promoter (-198 to +66) was sufficient for the Id-1-dependent suppression. Furthermore, the activity of the same promoter fragment (-198 to +66) was enhanced when antisense Id-1 expression vector was cotransfected. This osteocalcin gene promoter region contains two sites of an E-box motif, a consensus binding site for HLH proteins, which we refer to as OCE1 (CACATG, at -102) and OCE2 (CAGCTG, at -149), respectively. Mutagenesis in OCE1 but not OCE2 led to greater than 50% reduction in transcriptional activity of the osteocalcin gene promoter. Electrophoresis mobility shift assay indicated that factors in nuclear extracts prepared from ROS17/2.8 cells bound to the 30-bp oligonucleotide probe containing the E-box motif of OCE1. This binding was competed out by OCE1 oligonucleotide but neither by OCmE1 oligonucleotide in which E-box motif was mutated nor by OCE2. The OCE1-binding activity in the nuclear extracts of ROS17/2.8 cells was reduced by 70% when bacterially expressed Id-1 protein was added to the reaction mixture, suggesting the involvement of HLH proteins in the DNA/protein complex formation. In contrast to the osteoblast-like cells, OCE1-binding activity in the nuclear extracts of C3H10T1/2 fibroblasts was very low. However, when these fibroblasts were treated with recombinant human bone morphogenetic protein-2 which induced expression of osteocalcin as well as other phenotypic markers of osteoblasts, OCE1-binding activity was increased approximately 40-fold, indicating that OCE1 would be involved in the tissue-specific expression of the osteocalcin gene. These findings indicated for the first time that osteoblast-specific gene transcription is regulated via the interaction between certain E-box binding transcription factor(s) in osteoblasts and the OCE1 sequence in the promoter region of the osteocalcin gene.

Animals↗
PubMed1994

Possible involvement of lipoxygenase metabolites of arachidonic acid in the regulation of pregnenolone synthesis in bovine adrenocortical mitochondria.

Our previous investigations demonstrated that 5- and 15-lipoxygenase metabolites of arachidonic acid are synthesized in bovine adrenal fasciculata cells, although their exact role in the regulation of adrenal steroidogenesis is unknown. Thus we attempted to investigate their direct effects on cholesterol side-chain cleavage in bovine adrenal mitochondria. We also examined Ca2+ efflux in mitochondria, based on a reported correlation between pregnenolone formation and Ca2+ release in adrenal mitochondria. The present experiments showed that 5-HETE increased pregnenolone generation in the isolated intact mitochondria, but not in the inner mitochondrial membrane. Thus it is suggested that 5-HETE may activate cholesterol side-chain cleavage by inducing the translocation of cholesterol from the outer to the inner mitochondrial membrane. The present experiments also demonstrated that 5-HPETE, 5-HETE, 15-HPETE, and 15-HETE, but not leukotriene B4, activated cholesterol side-chain cleavage and Ca2+ efflux from mitochondria, suggesting that these substances may activate cholesterol side-chain cleavage by regulating Ca2+ movement in mitochondria. These effects were additively enhanced when mitochondria were stimulated simultaneously with these substances and GTP. Therefore, both GTP and lipoxygenase metabolites seem to play crucial roles in the regulation of pregnenolone generation. The direct effect of 5- and 15-lipoxygenase metabolites other than leukotriene B4 on the regulation of pregnenolone synthesis, which is known to be the rate-limiting step of steroidogenesis, were clearly observed in the present experiments.

Adrenal Cortex↗
PubMed1994

Purification and characterization of an acid phosphatase from Mycoplasma fermentans.

An acid phosphatase associated with the cell membranes of Mycoplasma fermentans was released from the membranes with Triton X-100, then purified by ion-exchange chromatography on DEAE-Sephacel and CM-Sepharose, followed by affinity chromatography on Con A-Sepharose. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified enzyme revealed a single band with a molecular mass of 31.2 kilodaltons. The enzyme activity toward p-nitrophenyl phosphate was enhanced remarkably by Cu2+, Co2+ and Mg2+, but the activity was not inhibited by EDTA. The enzyme dephosphorylated O-phospho-L-tyrosine as well as p-nitrophenyl phosphate, but not O-phospho-L-threonine, O-phospho-L-serine, glucose-1-phosphate, phosphoryl choline and adenosine triphosphate. The level of the O-phospho-L-tyrosine phosphatase activity was the highest in Mycoplasma faucium and the second highest in Mycoplasma fermentans of all tested human mycoplasmas.

Acid Phosphatase↗
PubMed1994

Purification and characterization of membrane protein (90 kDa) from Mycoplasma salivarium, which binds immunoglobulin (Ig) G Fc fragment.

A 90 kDa protein of Mycoplasma salivarium was released from cell membranes of the organism with Triton X-100 and purified by ion-exchange chromatography and chromatofocusing. The protein was eluted at pH 5.5 by chromatofocusing. The protein was shown to react with the Fc fragments of IgG from human and nine different animal species and did not distinguish between IgG from different species, while protein A, tested for comparative purposes, displayed a strong specificity for human and swine IgG. Furthermore, the protein reacted with antigen specific goat IgG (specific for gamma chains of human IgG), sheep red blood cells (SRBC) sensitized with rabbit antiserum to SRBC, that is, the Fc part of rabbit IgG, and concanavalin A as well. These findings may suggest that the protein is a lectin which binds the carbohydrate moiety of the Fc part of IgG.

Animals↗
PubMed1994

Maf nuclear oncoprotein recognizes sequences related to an AP-1 site and forms heterodimers with both Fos and Jun.

The v-maf oncogene, identified from AS42 avian retrovirus, encodes a nuclear bZip protein. To elucidate the molecular mechanism of cell transformation induced by this oncogene, we determined the specific binding sequences of its product. Maf protein recognized two types of relatively long palindromic consensus sequences, TGCTGACTCAGCA and TGCTGACGTCAGCA, at roughly equal efficiency. The middle parts of these Maf-binding sequences completely match with two binding sequences for AP-1 transcription factor, i.e., phorbol 12-O-tetradecanoate-13-acetate (TPA)-responsive element (TRE) and cyclic AMP responsive element, suggesting partial overlapping of the target genes for Maf and AP-1. Furthermore, Maf efficiently formed heterodimers with the components of AP-1, Fos and Jun, through their leucine zipper structures, and these heterodimers show binding specificities distinct from those for Maf-Maf and Jun-Jun homodimers. Thus, a multiple combination of the dimers should generate a greatly expanded repertoire of transcriptional regulatory potential. DNA data base search for the Maf-binding consensus sequences suggested that some of the TRE-like cis elements reported previously may actually be the targets for Maf family proteins or their heterodimers with other bZip proteins.

Animals↗
PubMed1994

MafB, a new Maf family transcription activator that can associate with Maf and Fos but not with Jun.

We have identified a new member of the maf oncogene family and named it mafB. This gene is expressed in a wide variety of tissues and encodes a protein of 311 amino acids containing a typical bZip motif in its carboxy-terminal region. In the bZip domain, MafB shares extensive homology not only with v-Maf but also with other Maf-related proteins. As expected from its structure, MafB forms a homodimer through its leucine repeat structure and specifically binds Maf-recognition elements (MAREs). In addition, MafB forms heterodimers with v-Maf and Fos through its zipper structure. However, unlike v-Maf, MafB fails to associate with Jun. Transient cotransfection assays revealed that both v-Maf and MafB act as transactivators for a promoter linked to MAREs, although MafB is less potent than v-Maf. As is the case for the c-maf gene, overexpression of the mafB gene induces transformation of chicken embryo fibroblasts in vitro. Through formation of numerous bZip dimers, the Maf family proteins along with the AP-1 components should provide great diversity in transcriptional regulation for a wide variety of genes.

3T3 Cells↗
PubMed1994

Cholera toxin can ADP-ribosylate Gs as well as Gi in ACTH-unresponsive human adrenocortical cancer.

It is well known that cholera toxin (CT) stimulates ADP-ribosylation of Gs and also pertussis toxin (PT) does Gi. Each GTP-binding protein has its own action in the regulation of adenylate cyclase. A human non-functioning adrenocortical cancer tissue showed an unresponsiveness in adenylate cyclase to ACTH although ACTH and CT activated adenylate cyclase in a non-functioning adrenal adenoma tissue. CT ADP-ribosylated 43 kDa protein of the plasma membrane of the cancer tissue while CT and PT could ADP-ribosylate 43 kDa and 38 kDa protein in the adenoma tissue, respectively. Immunoblotting analysis of the cancer tissue demonstrated that 40 kDa protein was detected by anti-Gs antibody as well as by anti-Gi antibody. The present experiments demonstrated that CT could ADP-ribosylate Gs which has stimulatory action on adenylate cyclase and also Gi which inhibits adenylate cyclase. Thus it is suggested that CT can activate the ADP-ribosylation of Gs and also Gi in a human adrenocortical cancer tissue, partly resulting in abnormal regulation of adenylate cyclase which may be crossly related to ACTH-unresponsiveness.

Adenoma↗