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At least 523 records · Page 29Linked to original sources
PubMed1993

A concise review: iron absorption--the mucin-mobilferrin-integrin pathway. A competitive pathway for metal absorption.

Newly identified iron binding proteins isolated from rat duodenal homogenates permit better understanding of iron absorption. Mucins bind iron at acid pH to keep iron soluble and available for absorption at the more alkaline pH of the duodenum; this explains iron deficiency following prolonged achlorhydria. Integrin (90/150 kD) was identified on the absorptive surface of enterocytes in association with radioiron and is believed to facilitate transit of iron through the microvillous membrane. Mobilferrin, a 56 kD iron binding protein, was isolated from enterocyte cytosol. It coprecipitates with integrin and appears in close association with integrins in the apical cytoplasm. We postulate it accepts dietary iron from integrin and acts as the shuttle protein for iron in the cytoplasm. Since iron in enterocytes remains in equilibrium with body stores, we postulate mucosal iron uptake is regulated by the number of iron binding sites either occupied or unoccupied by iron on mobilferrin. Iron repletion of enterocytes from body stores is accomplished via transferrin receptors on the posterolateral membranes of enterocytes. Increased transfer of iron from blood into absorptive enterocytes occurs in iron replete animals to inhibit mucosal uptake of dietary iron. Little transfer of iron from plasma to enterocytes occurs in iron deficiency. Enhanced mucosal transfer of iron into the body occurs with increased body need for iron. The exact mechanism for mucosal transfer of iron into the plasma has not been defined but may also be mediated by an integrin.

Absorption↗
PubMed1989

Primate spinothalamic pathways: I. A quantitative study of the cells of origin of the spinothalamic pathway.

In six monkeys spinothalamic (STT) cells were retrogradely labeled by injecting 2% wheat germ agglutinin-conjugated horseradish peroxidase into the somatosensory thalamus. Following a 5-day survival period, the animals were perfused and the tissue was removed and processed with the tetramethyl benzidine technique. In all animals there were HRP-labeled STT cells in all segments of the spinal cord. In one old world monkey, the injection included most of the thalamus and resulted in 18.235 estimated total number of STT cells. Of this total, 35% were located in the upper cervical segments (C1-C3), 18% were located in C4-C8, 19% were in the thoracic spinal cord with most found in T1-T3; 6% were in L1-L3, 13% were in L4-L7, and 7% were in the coccygeal segments. Of the total labeled STT cells, 17% were found in the spinal cord ipsilateral to the thalamic injections; 53% of these cells were located in C1-C3 primarily in lamina VIII. The percentage of label found in the contralateral lower cervical region laminae I-III (43-50%), IV-VI (33-48%), and VII-X (8-17%) was similar among three animals with similar thalamic injections. The distributions of the shapes of the labeled STT cells were similar for each lamina between the lower cervical and lower lumbar regions. The mean diameter of the labeled STT cells varied with spinal cord segment and lamina. The lamina I STT cells were the smallest. In the cervical spinal cord, lamina VIII STT cells had the largest diameters, while in the lumbar region laminae IV-VI had the largest STT cells.

Animals↗
PubMed2002

Inhibition of the p38 pathway upregulates macrophage JNK and ERK activities, and the ERK, JNK, and p38 MAP kinase pathways are reprogrammed during differentiation of the murine myeloid M1 cell line.

Mitogen-activated protein (MAP) kinases have been implicated as important mediators of the inflammatory response. Here we report that c-Jun NH(2)-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 MAP kinase activities are reprogrammed during the IL-6 induced macrophage-like differentiation of the murine myeloid M1 cell line. Moreover, p38 inhibition upregulates JNK and ERK activity in M1 cells and in thioglycollate-elicited peritoneal exudate macrophages. IL-6-induced M1 differentiation also induces expression of the anti-inflammatory cytokine IL-10, and p38 inhibition potentiates this increase in IL-10 expression in an ERK-dependent manner. Thus, we speculate that during inflammatory conditions in vivo macrophage p38 may regulate JNK and ERK activity and inhibit IL-10 expression. These data highlight the importance of p38 in the molecular mechanisms of macrophage function.

Animals↗
PubMed1989

Gamma interferon induces monocyte killing of Listeria monocytogenes by an oxygen-dependent pathway; alpha- or beta-interferons by oxygen-independent pathways.

Human peripheral blood monocytes purified by counterflow centrifugal elutriation were treated with recombinant interferons-gamma (IFN-gamma), alpha (IFN-alpha), or beta (IFN-beta)--and tested for their capacity to kill Listeria monocytogenes. All three IFNs increased the monocyte bactericidal activity in a dose-dependent fashion. Exogeneous catalase, an inhibitor of monocyte-generated hydrogen peroxide, did not affect bactericidal activity. However, exogenous superoxide dismutase inhibited killing by IFN-gamma-activated monocytes, but not by IFN-alpha- or IFN-beta-activated monocytes. By contrast, exogenous soybean trypsin inhibitor inhibited killing by IFN-alpha or IFN-beta-activated monocytes, but not by IFN-gamma-activated monocytes. Combinations of IFN-gamma and IFN-alpha resulted in no increase in bactericidal activity. Finally, treatment with IFN-gamma resulted in different receptiveness of the cell to subsequent oxidative burst-stimulating signals than did treatment with either IFN-alpha or IFN-beta. These results suggest that monocytes treated with IFN-gamma kill L. monocytogenes by an oxygen-dependent mechanism, but treatment with IFN-alpha or IFN-beta elicits principally oxygen-independent mechanisms.

Blood Bactericidal Activity↗
PubMed2002

Combinatorial signaling by an unconventional Wg pathway and the Dpp pathway requires Nejire (CBP/p300) to regulate dpp expression in posterior tracheal branches.

The decapentaplegic (dpp) gene influences many developmental events in Drosophila melanogaster. We have been analyzing dpp expression in two groups of dorsal ectoderm cells at the posterior end of the embryo, in abdominal segment 8 and the telson. These dpp-expressing cells become tracheal cells in the posterior-most branches of the tracheal system (Dorsal Branch10, Spiracular Branch10, and the Posterior Spiracle). These branches are not identified by reagents typically used in analyses of tracheal development, suggesting that dpp expression confers a distinct identity upon posterior tracheal cells. We have determined that dpp posterior ectoderm expression begins during germ band extension and continues throughout development. We have isolated the sequences responsible for these aspects of dpp expression in a reporter gene. We have determined that an unconventional form of Wingless (Wg) signaling, Dpp signaling, and the transcriptional coactivator Nejire (CBP/p300) are required for the initiation and maintenance of dpp expression in the posterior-most branches of the tracheal system. Our data suggest a model for the integration of Wg and Dpp signals that may be applicable to branching morphogenesis in other developmental systems.

Animals↗
PubMed1995

Conformational pathway of the polypeptide chain of chymotrypsin inhibitor-2 growing from its N terminus in vitro. Parallels with the protein folding pathway.

We have obtained a series of fragments growing from the N terminus of the protein chymotrypsin inhibitor-2 (C12) in order to study the development of structure on elongation of the polypeptide in solution. We present an extensive biophysical characterization of ten fragments using different conformational probes. Small fragments up to residue 40 of the 64-residue protein are disordered. Fragment (1-40) has non-native local hydrophobic clusters, but nevertheless does not bind 8-anilinonaphthalene-1-sulphonate (ANS). Hydrophobic regions in longer fragments become gradually more capable of binding ANS as the chain grows to completion, with a tendency to form native structures. Major changes in secondary structure and accessibility to hydrophobic sites occur in parallel, between (1-40) and (1-53), together with changes in hydrodynamic volume and flexibility. NMR studies of (1-53), the first fragment displaying tertiary interactions, show that a subcore is fully formed and the alpha-helix (residues 12 to 24) is of fluctuating structure. Fragments (1-53) and (1-60) share many properties with molten globule-like structures, with varying degrees or order. Fluorescence properties of the native fold are gradually recovered from fragments (1-60) to full-length C12, together with a decrease in hydrophobic exposure. A small degree of co-operativity of formation of structure appears when residue 60 is added, gradually increasing as residue 62 is added, but a full two-state co-operative transition appears only on addition of Arg62 and Val63. We believe this is the result of correct side-chain packing of the hydrophobic core, capping the major elements of secondary structure in C12 at this late stage, which is probed by the complete recovery of the fluorescence of the unique Trp5. The structures that develop as the polypeptide chain increases in length parallel the structural features present in the nucleus for the folding of intact protein, which develops in the transition state. The folding nucleus consists of much of the helix and the interactions made by Ala16 in the helix with residues in the core, especially with Leu49 and Ile57, with the rest of the structure being formed only very weakly in the transition state.

Amino Acid Sequence↗