scholarly journals Exogenous Cyclic AMP, Cholera Toxin, and Endotoxin Induce Expression of the Lipopolysaccharide Receptor CD14 in Murine Bone Marrow Cells: Role of Purinoreceptors

1999 ◽  
Vol 6 (6) ◽  
pp. 885-890 ◽  
Author(s):  
Thierry Pedron ◽  
Robert Girard ◽  
Richard Chaby
Keyword(s):  
Bone Marrow ◽  
Cyclic Amp ◽  
Cholera Toxin ◽  
Bone Marrow Cells ◽  
Specific Binding ◽  
Cell Surface Receptor ◽  
Intracellular Camp ◽  
Purine Derivatives ◽  
Murine Bone Marrow ◽  
Surface Receptor

ABSTRACT Little is known about the mechanisms of lipopolysaccharide (LPS) signaling in immature cells that do not express the LPS receptor CD14 yet. Bone marrow granulocytes do not constitutively express CD14 but can be stimulated by low doses of LPS in the absence of serum and then express an inducible form of LPS receptor (iLpsR). We show that in addition to LPS, cholera toxin (CT) and various cyclic AMP (cAMP) analogs can also induce the expression of iLpsR, which was identified as CD14. Induction was independent of intracellular cAMP. The hypothesis that cAMP analogs act via a cell surface receptor was suggested by the unresponsiveness of trypsin-treated cells to these inducers and by the specific binding of [3H]cAMP to the cells. This binding was not inhibited by LPS or CT but was inhibited by various purine derivatives. However, the receptor involved is not a conventional purinoreceptor since both an agonist and an antagonist of such receptors were able to induce iLpsR expression. The results suggest that cAMP analogs and other purine derivatives induce iLpsR after interaction with an unconventional, trypsin-sensitive, purinoreceptor distinct from LPS and CT receptors.

Pharmacological characterization of cyclic AMP receptors mediating gene regulation in Dictyostelium discoideum

1986 ◽  
Vol 6 (7) ◽  
pp. 2402-2408
Author(s):  
B Haribabu ◽  
R P Dottin
Keyword(s):  
Gene Expression ◽  
Cyclic Amp ◽  
Cell Surface ◽  
Dictyostelium Discoideum ◽  
Cell Surface Receptor ◽  
Intracellular Camp ◽  
Response Curves ◽  
Pharmacological Characterization ◽  
Surface Receptor ◽  
Extracellular Molecules

Extracellular molecules regulate gene expression in eucaryotes. Exogenous cyclic AMP (cAMP) affects the expression of a large number of developmentally regulated genes in Dictyostelium discoideum. Here, we determine the specificity of the receptor(s) which mediates gene expression by using analogs of cAMP. The order of potency with which these analogs affect the expression of specific genes is consistent with the specificity of their binding to a cell surface receptor and is distinct from their affinity for intracellular cAMP-dependent protein kinase. Dose-response curves with cAMP and adenosine 3',5'-monophosphorothioate, a nonhydrolyzable analog, revealed that the requirement for high concentrations of exogenous cAMP for regulating gene expression is due to the rapid degradation of cAMP by phosphodiesterase. The addition of low concentrations of cAMP (100 nM) or analogs in pulses also regulates gene expression. Both the genes that are positively regulated by exogenous cAMP and the discoidin gene, which is negatively regulated, respond to cAMP analogs to the same degree. Genes expressed in prespore or prestalk cells are also similarly regulated. These data suggest that the effects are mediated through the same receptor. The specificity of this receptor is indistinguishable from that of the well-characterized cell surface cAMP receptor.

scholarly journals Pharmacological characterization of cyclic AMP receptors mediating gene regulation in Dictyostelium discoideum.

1986 ◽  
Vol 6 (7) ◽  
pp. 2402-2408 ◽  
Author(s):  
B Haribabu ◽  
R P Dottin
Keyword(s):  
Gene Expression ◽  
Cyclic Amp ◽  
Cell Surface ◽  
Dictyostelium Discoideum ◽  
Cell Surface Receptor ◽  
Intracellular Camp ◽  
Response Curves ◽  
Pharmacological Characterization ◽  
Surface Receptor ◽  
Extracellular Molecules

Extracellular molecules regulate gene expression in eucaryotes. Exogenous cyclic AMP (cAMP) affects the expression of a large number of developmentally regulated genes in Dictyostelium discoideum. Here, we determine the specificity of the receptor(s) which mediates gene expression by using analogs of cAMP. The order of potency with which these analogs affect the expression of specific genes is consistent with the specificity of their binding to a cell surface receptor and is distinct from their affinity for intracellular cAMP-dependent protein kinase. Dose-response curves with cAMP and adenosine 3',5'-monophosphorothioate, a nonhydrolyzable analog, revealed that the requirement for high concentrations of exogenous cAMP for regulating gene expression is due to the rapid degradation of cAMP by phosphodiesterase. The addition of low concentrations of cAMP (100 nM) or analogs in pulses also regulates gene expression. Both the genes that are positively regulated by exogenous cAMP and the discoidin gene, which is negatively regulated, respond to cAMP analogs to the same degree. Genes expressed in prespore or prestalk cells are also similarly regulated. These data suggest that the effects are mediated through the same receptor. The specificity of this receptor is indistinguishable from that of the well-characterized cell surface cAMP receptor.

scholarly journals Thyroid and Bone: Macrophage-Derived TSH-β Splice Variant Increases Murine Osteoblastogenesis

Endocrinology ◽  
2013 ◽  
Vol 154 (12) ◽  
pp. 4919-4926 ◽  
Author(s):  
R. Baliram ◽  
A. Chow ◽  
A. K. Huber ◽  
L. Collier ◽  
M. R. Ali ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cho Cells ◽  
Bone Marrow Cells ◽  
Direct Interaction ◽  
Intracellular Camp ◽  
Bone Biology ◽  
New Paradigm ◽  
Murine Bone Marrow ◽  
Relative Contribution

It is now firmly established that TSH may influence the physiology and patho-physiology of bone by activating osteoblasts and inhibiting osteoclast activity resulting in relative osteoprotection. Whether this influence is directly exerted by pituitary-derived TSH in vivo is less certain, because we have previously reported that the suppression of pituitary TSH does not remove such protection. Here, we have characterized the functional relevance of a novel form of the TSH-β subunit, designated TSH-βv, known to be produced by murine bone marrow cells. We found that fresh bone marrow-derived macrophages (MØs) preferentially produced TSH-βv and, when cocultured with CHO cells engineered to overexpress the full-length TSH receptor, were able to generate the production of intracellular cAMP; a phenomenon not seen in control CHO cells, such results confirmed the bioactivity of the TSH variant. Furthermore, cocultures of MØs and osteoblasts were shown to enhance osteoblastogenesis, and this phenomenon was markedly reduced by antibody to TSH-β, suggesting direct interaction between MØs and osteoblasts as observed under the electron microscope. These data suggest a new paradigm of local modulation of bone biology by a MØ-derived TSH-like molecule and raise the question of the relative contribution of local vs pituitary-derived TSH in osteoprotection.

Identification of the SV2 protein receptor-binding site of botulinum neurotoxin type E

2013 ◽  
Vol 453 (1) ◽  
pp. 37-47 ◽  
Author(s):  
Stefan Mahrhold ◽  
Jasmin Strotmeier ◽  
Consuelo Garcia-Rodriguez ◽  
Jianlong Lou ◽  
James D. Marks ◽  
...  
Keyword(s):  
Binding Site ◽  
Synaptic Vesicle ◽  
Specific Binding ◽  
Cell Surface Receptor ◽  
Vesicle Membrane ◽  
Receptor Binding Site ◽  
Binding Interface ◽  
Protein Receptor ◽  
Surface Receptor ◽  
Extended Surface

The highly specific binding and uptake of BoNTs (botulinum neurotoxins; A–G) into peripheral cholinergic motoneurons turns them into the most poisonous substances known. Interaction with gangliosides accumulates the neurotoxins on the plasma membrane and binding to a synaptic vesicle membrane protein leads to neurotoxin endocytosis. SV2 (synaptic vesicle glycoprotein 2) mediates the uptake of BoNT/A and /E, whereas Syt (synaptotagmin) is responsible for the endocytosis of BoNT/B and /G. The Syt-binding site of the former was identified by co-crystallization and mutational analyses. In the present study we report the identification of the SV2-binding interface of BoNT/E. Mutations interfering with SV2 binding were located at a site that corresponds to the Syt-binding site of BoNT/B and at an extended surface area located on the back of the conserved ganglioside-binding site, comprising the N- and C-terminal half of the BoNT/E-binding domain. Mutations impairing the affinity also reduced the neurotoxicity of full-length BoNT/E at mouse phrenic nerve hemidiaphragm preparations demonstrating the crucial role of the identified binding interface. Furthermore, we show that a monoclonal antibody neutralizes BoNT/E activity because it directly interferes with the BoNT/E–SV2 interaction. The results of the present study suggest a novel mode of binding for BoNTs that exploit SV2 as a cell surface receptor.

p53-dependent and independent apoptosis induced by ionizing radiation in murine bone marrow cells

1997 ◽  
Vol 42 (2) ◽  
pp. 155-159
Author(s):  
Yufang Cui ◽  
Pingkun Zhou ◽  
Brian I. Lord ◽  
Jolyon H. Hendry
Keyword(s):  
Bone Marrow ◽  
Ionizing Radiation ◽  
Bone Marrow Cells ◽  
Murine Bone Marrow ◽  
Marrow Cells

Transformation of murine bone marrow cells with combined v-raf-v-myc oncogenes yields clonally related mature B cells and macrophages

1990 ◽  
Vol 10 (7) ◽  
pp. 3562-3568
Author(s):  
M Principato ◽  
J L Cleveland ◽  
U R Rapp ◽  
K L Holmes ◽  
J H Pierce ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Cell Lines ◽  
Bone Marrow Cells ◽  
Hematopoietic Differentiation ◽  
Developmental Relationships ◽  
Murine Bone Marrow ◽  
B Lineage ◽  
Marrow Cells

Murine bone marrow cells infected with replication-defective retroviruses containing v-raf alone or v-myc alone yielded transformed pre-B cell lines, while a retroviral construct containing both v-raf and v-myc oncogenes produced clonally related populations of mature B cells and mature macrophages. The genealogy of these transformants demonstrates that mature myeloid cells were derived from cells with apparent B-lineage commitment and functional immunoglobulin rearrangements. This system should facilitate studies of developmental relationships in hematopoietic differentiation and analysis of lineage determination.

Sign in / Sign up

Export Citation Format

Share Document