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Biomedical subjects

H Y Yang

Publications and source records attributed to H Y Yang.

At least 163 records · Page 9Linked to original sources

Keratin-like proteins that coisolate with intermediate filaments of BHK-21 cells are nuclear lamins.

Four proteins of Mr approximately equal to 60,000, 65,000, 67,000, and 70,000 coisolate with the major intermediate filament (IF) structural proteins of BHK-21 cells. These proteins are keratin-like, they form distinctive paracrystals in vitro, and they are concentrated at the nuclear surface. Since these properties indicate similarities with the nuclear lamins, we have prepared conventional fractions of BHK-21 nuclei from which the same type of paracrystal is obtained. Furthermore, biochemical and immunological data demonstrate that the lamins are identical to the Mr 60,000-70,000 proteins found in IF preparations, and both sets of proteins are similar to keratin. These results suggest that an IF-like protein network is present in the nuclear lamina. We speculate that in some unknown way this network connects to the cytoplasmic IF network that courses from the juxtanuclear region to the cell surface. These proposed interconnecting networks may form part of the infrastructure of cytoskeletal-nuclear matrix-connecting links involved in signal transmission between the nuclear and cytoplasmic compartments of eukaryotic cells.

Amino Acids↗

Splanchnic nerve transection abolishes the age-dependent increase of neuropeptide Y-like immunoreactivity in rat adrenal gland.

Using an antiserum directed against porcine neuropeptide Y (NPY), a high concentration of NPY immunoreactivity (NPY-IR) was detected in rat adrenal gland. The level of NPY-IR in the adrenal gland was found to increase considerably with age. Biochemical characterization by reverse-phase HPLC indicated that this increase was due to accumulations of NPY and another molecular form of NPY-like immunoreactive peptide. Chronic denervation of the splanchnic nerve abolished this age-dependent increase of NPY-IR rat adrenal gland.

Adrenal Glands↗

Effect of ethanol on human umbilical artery and vein in vitro.

In vitro effects of ethanol on human umbilical artery and vein were studied. Ethanol (0.5-2.0%) elicited a dose-dependent contractile response both in the umbilical arterial and venous strips in Krebs' and Ca2+-free Krebs' solution. In umbilical artery, but not in vein, ethanol shifted the CaCl2-induced dose-response curves to the right in a parallel manner along with a significant reduction in K+-depolarized maximal tension. These result demonstrate that ethanol can elicit a potent contractile response both in human umbilical arteries and veins and could aid in explaining why ethanol can induce the fetal alcohol syndrome.

Adult↗

Intermediate filament networks: organization and possible functions of a diverse group of cytoskeletal elements.

Immunofluorescence and electron microscopic observations demonstrate that intermediate filaments (IF) form cytoplasmic networks between the nucleus and cell surface in several types of cultured cells. Intermediate filaments interact with the nuclear surface, where they appear to terminate at the level of the nuclear envelope. From this region, they radiate towards the cell surface where they are closely associated with the plasma membrane. On the basis of these patterns of IF organization, we suggest that IF represent a cytoskeletal system interconnecting the cell surface with the nucleus. Furthermore, IF also appear to interact with other cytoskeletal components including microtubules and microfilaments. In the former case microtubule-IF interactions are seen in cytoplasmic regions between the nucleus and the cell membrane, whereas microfilament-IF interactions occur in the cortical cytoplasm. IF also appear to be cross-linked to each other; especially in the case of the IF bundles that occur in epithelial cells. In order to determine the molecular and biochemical bases of the organizational state of IF we have developed procedures for obtaining IF-enriched 'cytoskeletons' of cultured cells. In these preparations IF-nuclear and IF-cell surface associations are retained. Thus, these preparations have enabled us to begin to study various IF-associated structures (e.g. desmosomes) and associated proteins (IFAPs) using biochemical and immunological methodologies. To date, the results support the idea that IF and their associated proteins may comprise the cell type specific molecular infrastructure that is involved in transmitting and distributing information amongst the major cellular domains; the cell surface/extracellular matrix, the cytoplasm and the nuclear surface/nuclear matrix.

Actin Cytoskeleton↗

Inhibition of Met5-enkephalin-Arg6-Phe7 degradation by inhibitors of dipeptidyl carboxypeptidase.

The heptapeptide Met5-enkephalin-Arg6-Phe7 (YGGFMRF) is cleaved at a high rate by tissue peptidases including dipeptidyl carboxypeptidase. The inhibitor, Hoe 498 diacid (2-[N-[(S)-1-carboxy-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-2-azabicyclo- [3.3.0] octane-3-carboxylic acid), was found to be highly effective in blocking YGGFMRF degradation by a dipeptidyl carboxypeptidase present in a preparation of mouse striatal microsomes. The recovery of YGGFMRF released from rat striatal slices was increased in the presence of Hoe 498 diacid. Furthermore, the recovery of YGGFMRF injected into the caudate was increased in rats pretreated i.p. with Hoe 498 diacid. After i.v. or i.p. injections both Hoe 498 diacid and its prodrug Hoe 498 monoester (2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-2- azabicyclo [3.3.0] octane-3-carboxylic acid) were detected in rat cerebrospinal fluid and the dipeptidyl carboxypeptidase activity in cerebrospinal fluid was inhibited. These observations indicate that endogenously released YGGFMRF is protected from degradation by Hoe 498 diacid and that systemically administered Hoe 498 diacid or monoester penetrate the blood-brain barrier and inhibit brain and cerebrospinal fluid dipeptidyl carboxypeptidase activity. This potent inhibitor may be useful to block YGGFMRF inactivation in studies of the pharmacology and physiology of YGGFMRF. It is also possible that some of the cerebral effects of these compounds may be referable to an enhancement of YGGFMRF action in the central nervous system.

Animals↗

Biochemical and immunohistochemical evidence for the presence of motilin in pig cerebellum.

The presence of motilin in rat and porcine cerebellum was investigated by using high performance liquid chromatography (HPLC) coupled with radioimmunoassay or immunohistochemistry. The antibodies used for this study were raised against synthetic gastrointestinal porcine motilin, which is, so far, the only known sequence of this peptide. The results obtained show the presence of a sharp peak of motilin-like immunoreactivity after HPLC of porcine cerebellum extracts, with an elution time corresponding to that of synthetic porcine motilin. Motilin-like immunoreactivity was also detected immunohistochemically in porcine cerebellum. However no motilin-like immunoreactivity was detected in rat cerebellum biochemically or immunohistochemically. This finding suggests that if a motilin-like neuropeptide is present in rat cerebellum, its molecular form differs from that present in porcine cerebellum.

Animals↗

Interaction of alpha and beta adrenergic stimulation on aortic ornithine decarboxylase activity.

The interaction between beta and alpha adrenergic agonists on regulation of cockerel aortic ornithine decarboxylase (ODC) activity was examined. The beta adrenergic agonist isoproterenol both reduced basal aortic ODC activity and prevented induction of the decarboxylase by the alpha adrenergic agonist methoxamine. 3-Isobutyl-1- methylxanthine (IBMX) similarly reduced basal ODC activity and blocked induction of the enzyme by methoxamine. When given ten minutes before or after methoxamine, isoproterenol prevented aortic ODC induction, but not large sustained increases in blood pressure evoked by the alpha adrenergic agonist. In contrast, when injected three hours after methoxamine, isoproterenol had no effect on already elevated levels of enzyme activity. Addition of isoproterenol (10(-7)M), IBMX (1 mM) or dibutyryl cAMP (2.5 mM) to isolated aortic segments cultured in minimal salts-glucose media evoked decreases in basal levels of ODC activity resembling those observed in the intact animal. These results suggest that the balance between alpha and beta adrenergic stimulation may be an important feature of the regulation of polyamine biosynthesis in artery wall cells.

1-Methyl-3-isobutylxanthine↗

Release of NPY-like immunoreactive material from primary cultures of chromaffin cells prepared from bovine adrenal medulla.

In primary cultures of bovine chromaffin cells, the cell contents of NPY immunoreactive material was found to be stable for about 4 days. When these cells were transferred to the Locke's solution from the culture medium, NPY immunoreactive material was released spontaneously. Addition of potassium (45 mM) resulted in a 3-fold increase in the rate of NPY release in a calcium dependent fashion. NPY immunoreactivity in chromaffin cells is composed of NPY, a lesser immunoreactive peptide and two very minor immunoreactivities. The same immunoreactive peptides were released by 45 mM potassium.

Adrenal Medulla↗

Release of high molecular weight forms of met5-enkephalin-arg6-gly7-leu8 from rat brain.

The release of various molecular weight forms of met5-enk-arg6-gly7-leu8 (MERGL) from slices prepared from rat medulla-pons and hypothalamus was studied. The release of MERGL-IR from both medulla-pons and hypothalamic slices was elevated four- to ten-fold in response to potassium depolarization. Gel of 8 to 10 kilodalton MERGL-IR peptide(s), as well as MERGL itself, were released in response to stimulation with 50 mM K+.

Animals↗

Lymphocyte aging in allophenic mice.

Allophenic mice are chimeras which are produced from the aggregation of two genotypically distinct embryos. In this study, embryos from the C57BL/6J and A/J strains were used to produce C57BL/6J----A/J allophenic mice. These strains were chosen because of their markedly different lifespans, their different glucose phosphate isomerase (GPI) isozymes, and their different H-2 haplotypes [C57BL/6J: long-lived, Gpi-1b, H-2b; A/J: short-lived, Gpi-1a, H-2a]. The mice were bled at two month intervals and the composition of their peripheral blood lymphocytes determined at each point from analysis of GPI isozymes and H-2 antigens. It was found that the proportion of long-lived (C57BL/6J) lymphocytes tended to increase with age. Moreover, the total lifespan of the allophenic mice was directly related to the percentage of long-lived lymphocytes in their peripheral blood.

Aging↗

Isolation, sequencing, synthesis, and pharmacological characterization of two brain neuropeptides that modulate the action of morphine.

Two peptides that crossreact with an antiserum raised against Phe-Met-Arg-Phe-NH2 were purified from bovine brain extract. Their structures were determined to be Ala-Gly-Glu-Gly-Leu-Ser-Ser-Pro-Phe-Trp-Ser-Leu-Ala-Ala-Pro-Gln-Arg-Phe- NH2 and Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2. The sequences were determined by gas-phase sequencing, except for the COOH-terminal phenylalaninamides. These were assigned on the basis of the reactivity of the peptides with the anti-Phe-Met-Arg-Phe-NH2 antiserum, which appears to recognize the determinant -Arg-Phe-NH2. Both peptides were synthesized, and the synthetic peptides were found to have the same HPLC retention times as the endogenous Phe-Met-Arg-Phe-NH2-immunoreactive peptides, thus confirming the assignment of phenylalaninamide to the COOH-terminal positions. Both of the synthetic peptides were found to decrease tail-flick latency in rats, and the octapeptide was more active than the octadecapeptide. The octapeptide was found also to attenuate the prolongation of the tail-flick latency induced by morphine.

Amino Acid Sequence↗

The organizational fate of intermediate filament networks in two epithelial cell types during mitosis.

Intermediate filaments (IF) appear to be attached to the nuclear envelope in various mammalian cell types. The nucleus of mouse keratinocytes is enveloped by a cagelike network of keratin-containing bundles of IF (IFB). This network appears to be continuous with the cytoplasmic IFB system that extends to the cell surface. Electron microscopy reveals that the IFB appear to terminate at the level of the nuclear envelope, frequently in association with nuclear pore complexes (Jones, J. C .R., A. E. Goldman, P. Steinert, S. Yuspa, and R. D. Goldman, 1982, Cell Motility, 2:197-213). Based on these observations of nuclear-IF associations, it is of interest to determine the fate and organizational states of IF during mitosis, a period in the cell cycle when the nuclear envelope disassembles. Immunofluorescence microscopy using a monoclonal keratin antibody and electron microscopy of thin and thick sections of mitotic mouse keratinocytes revealed that the IFB system remained intact as the cells entered mitosis and surrounded the developing mitotic spindle. IFB were close to chromosomes and often associated with chromosome arms. In contrast, in HeLa, a human epithelial cell, keratin-containing IFB appear to dissemble as cells enter mitosis (Franke, W. W., E. Schmid, C. Grund, and B. Geiger, 1982, Cell, 30:103-113). The keratin IFB in mitotic HeLa cells appeared to form amorphous nonfilamentous bodies as determined by electron microscopy. However, in HeLa, another IF system composed primarily of a 55,000-mol-wt protein (frequently termed vimentin) appears to remain morphologically intact throughout mitosis in close association with the mitotic apparatus (Celis, J.E., P.M. Larsen, S.J. Fey, and A. Celis, 1983, J. Cell Biol., 97:1429-34). We propose that the mitotic apparatus in both mouse epidermal cells and in HeLa cells is supported and centered within the cell by IFB networks.

Animals↗

A 300,000-mol-wt intermediate filament-associated protein in baby hamster kidney (BHK-21) cells.

Native intermediate filament (IF) preparations from the baby hamster kidney fibroblastic cell line (BHK-21) contain a number of minor polypeptides in addition to the IF structural subunit proteins desmin, a 54,000-mol-wt protein, and vimentin, a 55,000-mol-wt protein. A monoclonal antibody was produced that reached exclusively with a high molecular weight (300,000) protein representative of these minor proteins. Immunological methods and comparative peptide mapping techniques demonstrated that the 300,000-mol-wt species was biochemically distinct from the 54,000- and 55,000-mol-wt proteins. Double-label immunofluorescence observations on spread BHK cells using this monoclonal antibody and a rabbit polyclonal antibody directed against the 54,000- and 55,000-mol-wt proteins showed that the 300,000-mol-wt species co-distributed with IF in a fibrous pattern. In cells treated with colchicine or those in the early stages of spreading, double-labeling with these antibodies revealed the co-existence of the respective antigens in the juxtanuclear cap of IF that is characteristic of cells in these physiological states. After colchicine removal, or in the late stages of cell spreading, the 300,00-mol-wt species and the IF subunits redistributed to their normal, highly coincident cytoplasmic patterns. Ultrastructural localization by the immunogold technique using the monoclonal antibody supported the light microscopic findings in that the 300,000-mol-wt species was associated with IF in the several physiological and morphological cell states investigated. The gold particle pattern was less intimately associated with IF than that defined by anti-54/55 and was one of non-uniform distribution along IF, being clustered primarily at points of proximity between IF, where an amorphous, proteinaceous material was often the labeled element. Occasionally, "bridges" of label were seen extending outward from such clusters on IF. Gold particles were infrequently bound to microtubules, microfilaments, or other cellular organelles, and when so, IF were usually contiguous. During multiple cycles of in vitro disassembly/assembly of the IF from native preparations, the 300,000-mol-wt protein remained in the fraction containing the 54,000- and 55,000-mol-wt structural subunits, whether the latter were in the soluble state or pelleted as formed filaments. In keeping with the nomenclature developed for the microtubule-associated proteins (MAPs), the acronym IFAP-300K (intermediate filament associated protein) is proposed for this molecule.

Animals↗

Purification of the 300K intermediate filament-associated protein and its in vitro recombination with intermediate filaments.

IFAP-300K is a 300,000-mol-wt intermediate filament-associated protein previously identified in the baby hamster kidney fibroblastic cell line (BHK-21) by a monoclonal antibody (Yang H.-Y., N. Lieska, A. E. Goldman, and R. D. Goldman, 1985, J. Cell Biol., 100: 620-631). In the present study, this molecule was purified from the high salt/detergent-insoluble cytoskeletal preparation of these cells. Gel filtration on Sephacryl S-400 in the presence of 7.2 M urea allowed separation of the high molecular weight fraction from the structural intermediate filament (IF) subunits desmin and vimentin, designated 54K and 55K, respectively, and other low molecular weight polypeptides. DE-52 cellulose chromatography of the high molecular weight fraction using a linear NaCl gradient in 8 M urea yielded a pure 300,000-mol-wt species which was confirmed to be IFAP-300K by immunological and peptide mapping criteria. Two-dimensional PAGE of native BHK IF preparations followed by immunoblot analysis demonstrated the inability of the IFAP-300K-immunoreactive material to enter the first dimensional gel except as a 200,000-mol-wt doublet which presumably represented a major proteolytic derivative of IFAP-300K. The molecule's pl of 5.35, as determined by chromatofocusing, and its amino acid composition were extremely similar to those of BHK cell vimentin/desmin despite their non-identity. Ultrastructurally, IFAP-300K preparations in low salt buffers existed as particles composed of one or two elliptical units measuring 16 X 20 nm. In physiological salt buffers, the predominant entities were large, elongated aggregates of the elliptical units, which were able to be decorated by using the immunogold technique with monoclonal anti-IFAP-300K. Compared with the morphology of homopolymer vimentin IF, in vitro recombination studies using column-purified vimentin and IFAP-300K demonstrated the additional presence of aggregates similar in appearance to IFAP-300K at points of contact between IFs. Antibody decoration and immunogold labeling of these recombined preparations using rabbit antidesmin/vimentin and monoclonal anti-IFAP-300K confirmed the identity of the inter-filament, amorphous material as IFAP-300K. The presence of IFAP-300K at many points of intersection and lateral contact between IFs, as well as at apparent inter-filament "bridges," in these recombined specimens was identical to that seen both in situ and in native IF preparations. No such co-sedimentation was found in vitro between actin and IFAP-300K. No effects of IFAP-300K upon the kinetics of IF polymerization were detected by turbidimetric measurements.

Amino Acids↗

Neuropeptide Y in bovine adrenal glands: distribution and characterization.

Neuropeptide Y (NPY) distribution in bovine adrenal glands was studied by RIA and immunohistochemical technique. NPY content (picomoles per mg protein +/- SEM) of chromaffin cells, medulla, cortex, and whole glands was 4.2 +/- 0.16, 2.7 +/- 0.28, 0.19 +/- 0.02, and 0.94 +/- 0.14, respectively, while the chromaffin granule NPY content was 53. Immunohistochemically, NPY immunoreactivity was detected in norepinephrine containing chromaffin cells and also in nerve fibers crossing through adrenal cortex and medulla. NPY and enkephalin immunoreactivities were found in distinct chromaffin cells. Biochemical characterization by HPLC revealed two major NPY immunoreactive peptides. The most abundant molecular form was identified as authentic NPY.

Adrenal Glands↗