Biomedical subjects

C Tanaka

Publications and source records attributed to C Tanaka.

At least 19 recordsLinked to original sources

PubMed1992

Augmentation of retinoic acid-induced granulocytic differentiation in HL-60 leukemia cells by serine/threonine protein phosphatase inhibitors.

To evaluate the involvement of protein phosphatases (PP) in differentiation of human myelogenous leukemia HL-60 cells, we made use of potent inhibitors of PP1 and PP2A, calyculin-A (CAL-A) and okadaic acid (OKA). CAL-A and OKA could augment all-trans retinoic acid (ATRA)-induced granulocytic differentiation, whereas the differentiation toward macrophage lineage by 12-o-tetradecanoylphorbol acetate (TPA) was unchanged in the presence of CAL-A. CAL-A augmented the phosphorylation of 18K, 23K and 30K proteins induced by ATRA. The PP1 and PP2A were identified and were present mainly in the cytosol of HL-60 cells. These results suggest that either PP1 or PP2A or both may be involved in regulating granulocytic differentiation of HL-60 cells.

Cell Adhesion↗

PubMed1992

Molecular cloning and characterization of the promoter region of the calcineurin A alpha gene.

The 5'-flanking region of the calcineurin A alpha gene was isolated from a rat genomic library. It lacked TATA and CAAT boxes but contained G+C-rich regions, and was demonstrated to function as a strong promoter in neuronal cell lines (NG108-15 mouse neuroblastoma x rat glioma hybrid cells or N1E115 mouse neuroblastoma cells), but not in nonneuronal cell lines (C6 rat glioma or L-M mouse fibroblastoid cells) in a transient chloramphenicol acetyltransferase expression assay. Deletion analysis of the 5'-flanking region revealed that the core promoter region, as well as the sequence critical for cell-type-specific-promoter function, reside within the fragment -107 to +157 with respect to the major transcription initiation site.

Amino Acid Sequence↗

PubMed1992

The loss of beta II-protein kinase C in the striatum from patients with Huntington's disease.

We have examined the levels of protein kinase C (PKC) in autopsied brains of patients with Huntington's disease (HD), using [3H]4-beta-phorbol-12,13-dibutyrate ([3H] PDBu) and antisera against the PKC subspecies. In the caudate nucleus and putamen from patients with HD, the specific binding for [3H]PDBu was significantly decreased by 74 and 68%, respectively, as compared to findings in controls. The beta II-PKC immunoreactivities were significantly reduced by 65%, whereas the alpha-PKC immunoreactivities increased by 146%, in the putamen. There were no differences in the beta I- or gamma-PKC immunoreactivities in the putamen between HD and controls. These results suggest the differential localization of four PKC subspecies in human striatum and the involvement of four subspecies in different aspects of HD pathophysiology.

Brain↗

PubMed1992

Molecular structure of the C beta catalytic subunit of rat cAMP-dependent protein kinase and differential expression of C alpha and C beta isoforms in rat tissues and cultured cells.

A full-length cDNA clone encoding the C beta catalytic subunit of cAMP-dependent protein kinase (PKA) was isolated from a rat brain cDNA library. A 1.1 kb cDNA containing the entire coding region encodes for a protein of 351 amino acids that shows more than 95% sequence homology to the C beta subunits in mouse, bovine and human. Northern blot analysis showed distinct patterns of C alpha and C beta mRNA expression in the brain and various peripheral tissues. The C alpha mRNA was widespread and highly expressed in brain, heart, adrenal gland, testis, lung, kidney, spleen and liver, whereas the C beta mRNA was unevenly expressed in the brain and adrenal gland and in much lesser amounts in other tissues. The C alpha mRNA was evenly distributed and highly expressed through various regions of the brain, while the C beta mRNA was expressed in lesser amounts and was unevenly distributed. In neuronal and glial cultured cells, C alpha mRNA was also predominantly expressed but C beta mRNA was undetectable. The differential distribution between the C subunit isoforms of PKA suggests that individual subunits are involved in specialized functions.

Amino Acid Sequence↗

PubMed1992

cDNA cloning of a neural visinin-like Ca(2+)-binding protein.

A 21,000-dalton Ca(2+)-binding protein (Walsh, M.P., Valentine, K.A., Ngai, P.K., Carruthers, C.A., and Hollengerg, M.D. (1984) Biochem. J. 224, 117-127) was purified from the rat brain and through the use of oligonucleotide probe based on partial amino acid sequence, cDNA clones were obtained from rat brain cDNA library. The complete amino acid sequence deduced from the cDNA contains 191 residues and has a calculated molecular mass of 22,142 daltons. There are three potential Ca(2+)-binding sites like the EF hands in the sequence. It displays striking sequence homology with visinin and recoverin, retina-specific Ca(2+)-binding proteins. Northern blot analysis revealed that the protein is highly and specifically expressed in the brain.

Amino Acid Sequence↗

PubMed1992

The suppression of olfactory bulbectomy-induced muricide by antidepressants and antihistamines via histamine H1 receptor blocking.

The effects of antidepressants [(+)-oxaprotiline, (-)-oxaprotiline, imipramine, maprotiline, and trazodone] and antihistamines (mepyramine, dimethindene, ketotifen, methapyrilene, and antazoline) on muricidal behaviour in olfactory bulbectomized rats were investigated. All drugs except for dimethindene, which only minimally passes across the blood-brain barrier, suppressed muricide. The drugs which have high affinity for histamine H1 receptor showed potent suppressive effect on muricide. It is suggested that the central histaminergic system is involved via H1 receptors in the expression of muricide in olfactory bulbectomized rats.

Aggression↗

PubMed1992

Localization of subspecies of protein kinase C in the mammalian central nervous system.

Activation of protein kinase C (PKC) is regulated by dual second messengers; diacylglycerol (DG) produced by receptor mediated hydrolysis of phosphatidylinositol and Ca2+ which is released by inositol 1,4,5-triphosphate (IP3) from intracellular stores in the endoplasmic reticulum. In the mammalian central nervous system, available evidence suggests that PKC plays a prominent role in the processing of neuronal signals and in the short-term or long-term modulation of synaptic transmission. This enzyme is a member of a family consisting of at least eight subspecies, alpha, beta I, beta II, gamma, delta, epsilon, zeta and eta. The homologous structure of each subspecies makes difficult resolution of the enzymological properties of the enzyme. The distinct functional roles of PKC subspecies in mammalian tissues have been elucidated by defining the localization of each subspecies. We identified alpha-, beta I-, beta II- and gamma-PKC subspecies in the rat brain by in situ hybridization and by light and electron microscopic immunohistochemistry, using antibodies specific for each subspecies. Most immunoreactions of the alpha, beta I, beta II and gamma subspecies were evident in neurons and there were few, if any, in glial cells. In this article, we summarize known cellular and subcellular localizations of PKC subspecies in mammalian CNS and some aspects of current studies in neuronal functions regulated by this enzyme are discussed.

Amino Acid Sequence↗

PubMed1992

cDNA cloning and tissue distribution of a rat ubiquitin carboxyl-terminal hydrolase PGP9.5.

We have isolated a cDNA clone encoding ubiquitin carboxyl-terminal hydrolase PGP9.5 from a rat brain cDNA library and examined the tissue distribution. The primary structure of the cDNA consists of 856 nucleotides including the entire coding region for 223 amino acids, and the calculated molecular mass is 24,782 Da. The rat PGP9.5 is strikingly homologous to the human PGP9.5, 75.2% of nucleic acids and 95.1% of amino acids being identical. The mRNA of PGP9.5 is most abundant in the rat brain and to a lesser degree in the testis. In other peripheral tissues we tested, the mRNA was undetectable. Western blotting using an anti-rat PGP9.5 antibody revealed the parallel distribution of mRNA and protein in various brain regions and testis. The availability of the rat PGP9.5 clone provides a new approach to examine the function of PGP9.5 and the role that it plays in the pathology of neurodegenerative diseases.

Amino Acid Sequence↗

PubMed1992

Distinct cellular expression of calcineurin A alpha and A beta in rat brain.

Specific polyclonal antibodies that distinguish the two distinct isoforms of the catalytic subunit of calmodulin-dependent protein phosphatase, calcineurin A alpha and A beta, were prepared, and the distribution of calcineurin A alpha and A beta in rat brain was studied using immunochemical and immunocytochemical techniques. Immunochemical measurement revealed that the regional distributions of the two isoforms differed and that A alpha was more abundant than A beta in the rat brain. The subcellular distribution patterns of both isoforms were similar. Both isoforms were highly enriched in cytosolic fractions, including the synaptosomal cytosol. Immunocytochemical analysis revealed that both A alpha and A beta immunoreactivities differed in regional and cellular localizations. These different patterns of expression suggest that the two isoforms of calcineurin A may each have specific functions in modulating neuronal activity in particular cell types.

Animals↗

PubMed1992

Evidence for distinct neuronal localization of gamma and delta subunits of Ca2+/calmodulin-dependent protein kinase II in the rat brain.

Localization of the gamma and delta types of mRNAs for Ca2+/calmodulin-dependent protein kinase II (CaM-kinase II) was determined in the rat brain, making use of in situ hybridization histochemistry. The gamma and delta mRNAs as well as the alpha and beta mRNAs for CaM-kinase II were heterogeneously and distinctly distributed. In the Purkinje cell layer of the cerebellum, alpha, beta, and gamma mRNAs but not delta mRNA were present, whereas beta, gamma, and delta mRNAs were present in the locus coeruleus. These findings provide evidence that CaM-kinase II exists in a variety of forms in different cells composed of a variable number and type of subunits.

Animals↗

PubMed1992

Synthesis and evaluation of iodinated benzamide derivatives as selective and reversible monoamine oxidase B inhibitors.

A new series of iodinated analogues of N-(2-aminoethyl)benzamide was synthesized and evaluated for inhibitory potency and specificity toward monoamine oxidase type-B (MAO-B). Among them, N-(2-aminoethyl)-2-chloro-4-iodobenzamide hydrochloride (2d) showed high inhibitory potency and selectivity against MAO-B. The type of MAO-B inhibition by 2d was non-competitive and the inhibition constant (Ki) was 0.80 microM. Strong and selective in vivo MAO-B inhibition by 2d was also confirmed. The brain MAO-B inhibition by 2d was reversible and the enzyme activity completely returned to the control value 24 h after administration. Compound 2d was, therefore, considered to be a candidate for advanced development as a radioiodinated ligand that may be useful for functional MAO-B studies in the living brain using single photon emission computer tomography.

Animals↗

PubMed1992

Synthesis and aldose reductase inhibitory activities of benzyl 2-oxazolecarbamate analogues.

Various analogues of benzyl 5-phenyl-2-oxazolecarbamate (1a) were synthesized, and the structure-activity relationship of these analogues as aldose reductase inhibitor was studied. The carbamate group was necessary for the inhibitory activity. The introduction of an alkyl group at the C-4 position of 1a enhanced the inhibitory activity, however, the N-carboxymethyl group on the carbamate moiety counteracted to a hydrophobic interaction between the alkyl group at the C-4 position and the enzyme molecule.

Aldehyde Reductase↗

PubMed1992

Follicular bronchiolitis associated with rheumatoid arthritis.

Follicular bronchiolitis is a rare disorder, though it has been recognized as a pulmonary involvement of rheumatoid arthritis in recent years. A 57-year-old woman with rheumatoid arthritis was admitted to the hospital with persistent productive cough and breathlessness on exertion. An open lung biopsy was performed to establish a definite pathologic diagnosis of her disease, and she was diagnosed as having follicular bronchiolitis on the basis of the histopathological findings. It is essential to differentiate this disease from other bronchiolar or lymphoproliferative disorders of the lung.

Arthritis, Rheumatoid↗

PubMed1991

Effects of L-threo-DOPS, a noradrenaline precursor, on the long-term potentiation in the rat hippocampal mossy fiber-CA3 region.

The effects of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), a synthetic precursor of norepinephrine (NE), on the long-term potentiation (LTP) in the hippocampal mossy fiber-CA3 system was examined in urethane-anesthetized rats, the objective being to determine whether or not this drug acts as NE on the LTP. L-threo-DOPS may be effective for treating some type of mental disorders, including dementia. The LTP, induced in CA3 by tetanic stimulation (100 Hz for 1 s) applied to the mossy fiber persisted for more than 4 h. When L-threo-DOPS (50 and 150 micrograms) was injected into the lateral ventricle 30 min prior to the tetanic stimulation, there were no significant alterations in the LTP. However, in animals treated with reserpine (5 mg/kg i.p.) 24 h before the experiment, LTP was not induced with tetanic stimulation alone yet was obtained when tetanic stimulation was preceded by L-threo-DOPS (50 and 150 micrograms) applied to the ventricle. The LTP obtained by L-threo-DOPS in the reserpine-treated animal was inhibited by pretreatment with benserazide and was completely blocked by the simultaneous administration of sotalol. These results suggest that NE converted from L-threo-DOPS plays an important role in inducing LTP in the mossy fiber-CA3 system in the animals deficient in catecholamines.

Anesthesia↗

PubMed1991

cDNA cloning of a calcineurin B homolog in Saccharomyces cerevisiae.

We have isolated a cDNA clone encoding a homolog of mammalian calcineurin B (the regulatory subunit of calmodulin-dependent protein phosphatase) by screening a cDNA expression library of Saccharomyces cerevisiae with antiserum against bovine calcineurin B. The yeast calcineurin B homolog (YCNB) is composed of 175 amino acids with a calculated molecular mass of 19,639 daltons and contains four putative Ca(2+)-binding domains. The amino-acid alignment of YCNB with human calcineurin B demonstrates 53% sequence identity and 82% homology. Southern blot analysis indicates that the gene for YCNB is a single-copy gene. Thus, yeast calmodulin-dependent protein phosphatase apparently has a heterodimeric structure similar to that of the enzyme in mammalians.

Amino Acid Sequence↗

PubMed1991

Differential expression of the beta I- and beta II-PKC subspecies in the postnatal developing rat brain; an immunocytochemical study.

Differential expression of protein kinase C subspecies, beta I- and beta II-PKC, derived from a single gene by alternative splicing was evidenced in the postnatal developing rat brain. Immunoblot analysis of the PKC subspecies in the whole developing brain showed that beta I-PKC was present at birth and then gradually increased, while beta II-PKC was not present at birth or on postnatal day 3, then increased rapidly from day 7 to the maximum value seen in the adult brain. Under light microscopy, beta I-PKC immunoreactivities seen at birth were the most intense in the brainstem and intense in the diagonal bundle and globus pallidus. beta I-PKC immunoreactivities in these neurons weakened from day 7 and disappeared in the adult brain, while in the cerebral cortex, triangular septal nucleus and pontine nucleus beta I-PKC immunoreactivities were week at birth and then gradually increased. beta II-PKC immunoreactivities were first visible in neurons on day 7 and increased progressively. beta I- and beta II-PKCs were not co-localized in a neuron, as far as examined. The immunoreactivities of beta I-PKC at birth were localized in growth cone-like structures as well as in the dendrites and perikarya. Similarly, alpha-PKC was also present at birth in the growth cone-like structure. Immunoblot analysis revealed that beta I-PKC was present at birth in the growth cone-rich fraction from the hindbrain but not in that from the forebrain, while alpha-PKC was found in the growth cone-rich fraction from both the forebrain and the hindbrain. beta II- and gamma-PKC were not detected in the growth cone-rich fraction from either forebrain or hindbrain. These findings suggest that beta I- and beta II-PKC play a role in different stages of development and in different neurons; both beta-subspecies may be involved in postnatal developing neuronal functions while only beta I-PKC plays functional roles in the growth cone, in the prenatal developmental stage.

Aging↗

PubMed1991

Structural study of aldose reductase inhibitors. Ten oxazolecarbamate derivatives.

(1) Benzyl 4-isopropyl-5-phenyl-2-oxazolecarbamate, C20H20N2O3, Mr = 336.39, P1, a = 19.469 (7), b = 11.270 (3), c = 8.667 (3) A, alpha = 95.48 (3), beta = 99.61 (3), gamma = 104.96 (3) degrees, V = 1792 (1) A3, Z = 4, Dm = 1.266 (2), Dx = 1.247 g cm-3, lambda (Cu K alpha) = 1.5418 A, mu = 6.49 cm-1, F(000) = 712, T = 288 K, R = 0.048 for 5244 reflections. (2) Benzyl 4-ethyl-5-phenyl-2-oxazolecarbamate, C19H18N2O3, Mr = 322.37, P2(1)/n, a = 9.131 (7), b = 18.81 (1), c = 9.680 (8) A, beta = 101.07 (3) degrees, V = 1631 (2) A3, Z = 4, Dm = 1.310 (2), Dx = 1.313 g cm-3, lambda (Cu K alpha) = 1.5418 A, mu = 6.92 cm-1, F(000) = 680, T = 288 K, R = 0.063 for 2535 reflections. (3) Benzyl 4-methyl-5-phenyl-2-oxazolecarbamate, C18H16N2O3, Mr = 308.34, P2(1)/n, a = 9.210 (7), b = 8.785 (6), c = 19.800 (9) A, beta = 99.60 (3) degrees, V = 1580 (2) A3, Z = 4, Dm = 1.299 (3), Dx = 1.300 g cm-3, lambda (Cu K alpha) = 1.5418 A, mu = 6.93 cm-1, F(000) = 648, T = 288 K, R = 0.057 for 2190 reflections.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗

PubMed1991

cDNA cloning of a novel testis-specific calcineurin B-like protein.

A cDNA clone encoding a novel calcineurin B-like protein (CBLP) was isolated from a rat testis cDNA library by cross-hybridization with a calcineurin B cDNA probe. CBLP is composed of 176 amino acids and contains four putative Ca(2+)-binding domains. The overall predicted amino acid sequence homology between CBLP and calcineurin B is 82%. Northern blots showed that transcripts for CBLP are specifically and highly expressed in the testis.

Amino Acid Sequence↗