Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the chemotactic peptide receptor/cytoskeletal interactions in HL-60 cells induced to differentiate with different agents and attempted to correlate these observations with the acquisition of different functional responses. Dibutyryl cyclic AMP-treated cells showed rapid superoxide anion production in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) and slow, sustained response to phorbol myristate acetate (PMA). Retinoic acid-induced cells showed a slow, sustained response to both FMLP and PMA. Interferon-gamma-treated cells produced no superoxide anion on stimulation with FMLP, whereas tumor necrosis factor (TNF)-treated cells showed a slight response. Chemotactic peptide receptor association was the same in the HL-60 cells treated with different agents, despite marked differences in the superoxide anion generation and actin polymerization responses to FMLP and PMA in these cells. In mature neutrophils chemotactic peptide receptor association with the cytoskeleton was not affected by either pertussis or cholera toxin. However, both toxins inhibited FMLP-induced actin polymerization and superoxide anion generation. This suggested involvement of a G-protein similar to Gt, rather than Gi or Gs. Neither toxin had any effect on PMA-induced superoxide anion generation. These observations indicate that receptor association with the cytoskeleton may not have a significant role in affecting signal recognition and response. Among the several possible roles suggested, clearance of the occupied receptors may be the most important role of the cytoskeletal association. HL-60 cells induced to differentiate with different agents (because of their varied functional responses) might prove very useful in dissecting the molecular mechanisms regulating stimulus-induced activation of neutrophils.
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PMID:Chemotactic peptide receptor-cytoskeletal interactions and functional correlations in differentiated HL-60 cells and human polymorphonuclear leukocytes. 255 Apr 79

Retinoic acid rapidly induces the accumulation of a specific enzyme, tissue transglutaminase (EC 2.3.2.13), in mouse macrophages. We have used the induction of tissue transglutaminase to study the regulation of gene expression by retinoic acid. In this study we report that pertussis toxin can inhibit retinoic acid-induced expression of tissue transglutaminase in mouse resident peritoneal macrophages. This inhibition is paralleled by the ADP-ribosylation of 41,000-dalton macrophage membrane protein.
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PMID:Pertussis toxin inhibits retinoic acid-induced expression of tissue transglutaminase in macrophages. 287 93

Retinoic acid-induced differentiation of human leukemic HL-60 cells is accompanied with the early induction of an ecto-enzyme of NAD+ glycohydrolase (NADase), which has recently been identified as human leukocyte cell surface antigen CD38 [Kontani, K. et al. (1993) J. Biol. Chem. 268, 16895-16898]. The terminal cell differentiation attendant upon the cell growth arrest was, but the early induction of CD38 NADase activity was not, inhibited by prior treatment of HL-60 cells with pertussis toxin, which catalyzed ADP-ribosylation of the membrane-bound alpha beta gamma-trimeric GTP-binding proteins. The prior treatment was, however, not essential for the toxin-induced inhibition of the cell differentiation; the inhibition by the addition of pertussis toxin was still observed even after retinoic acid-induced expression of CD38 antigen. This suggested that a pertussis toxin-sensitive mechanism was involved in a late process of cell differentiation. Indeed, HL-60 cells appeared to secrete a differentiation-supporting factor in response to retinoic acid, since the cell differentiation was accelerated and potentiated upon culture of the cells in a conditioned medium prepared from retinoic acid-treated cells. The action of the differentiation-supporting factor was destroyed by heating and markedly attenuated in pertussis toxin-pretreated HL-60 cells. Thus, the whole process of the retinoic acid-induced cell differentiation appeared to consist of two distinguishable periods in terms of sensitivity to pertussis toxin; the toxin-insensitive early period characterized by the induction of CD38 NADase activity and the toxin-sensitive late period in which the secretion of a differentiation-supporting factor might be involved.
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PMID:Involvement of pertussis toxin-sensitive mechanism in retinoic acid-induced differentiation of human leukemic HL-60 cells. 777 89

Culture of mouse resident peritoneal macrophages with retinoic acid resulted in increased expression of the tissue transglutaminase gene as revealed by increases in the maximal velocity of the enzyme reaction in the cytosol and in the enzyme mRNA level. Protein kinase C-activating phorbol esters and okadaic acid, both of which were without effect on the enzyme induction by themselves, enhanced the retinoic acid-induced gene expression, which was in turn inhibited partially by pertussis toxin and totally by inhibitors of protein kinase C in either the presence or absence of phorbol esters. Retinoic acid was more effective in the "conditioned" medium, in which macrophages had been cultured for a time longer than 4 h, than in the "fresh" medium. The retinoic acid induction of transglutaminase was accompanied by increased phosphatidylinositol turnover and phosphatidic acid generation, which were efficiently suppressed by prior exposure of cells to pertussis toxin. It is likely that certain autocrine factor(s) liberated during culture of macrophages may afford conditions favorable for retinoic acid-induced gene expression, presumably via pertussis toxin-sensitive G protein-mediated phosphoinositide metabolism leading to activation of protein kinase C.
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PMID:Retinoic acid-induced gene expression of tissue transglutaminase via protein kinase C-dependent pathway in mouse peritoneal macrophages. 798 4

Retinoic acid (RA) treatment of F9 murine teratocarcinoma (TC) cells reduces the expression of the protein kinase A (PKA)-associated G protein, G alpha i2. The present study reveals interactions between the RA and PKA pathways during differentiation of the multipotent human TC cell line NTERA-2 clone D1 (abbreviated NT2/D1) which differ from prior reports in F9 TC cells. Compared to untreated NT2/D1 cells, differentiated NT2/D1 cells expressed increased levels of G alpha s and G alpha i1,2 proteins as shown by both immunoblot analysis and cholera toxin- and pertussis toxin-induced ADP ribosylation. To further explore cooperation between these pathways during human TC differentiation, we examined the effects of cyclic adenosine monophosphate (cAMP) on RA-responsive genes and of RA treatment on the transcriptional activation of a cAMP response element (CRE). Compared to RA alone, combined treatment with RA and cAMP augmented the expression of the RA nuclear receptor-beta (RAR-beta). Also, transient transfection assays revealed that cAMP and RA cooperated to enhance CRE transcriptional activation. The cAMP-induced enhancement of RA actions in NT2/D1 cells extended to immunophenotypic changes typical of the neuronal differentiation program induced by RA. In contrast to these findings in NT2/D1 cells, prior work in F9 TC cells showed that cAMP inhibits the RA-mediated augmentation of RAR-beta expression and switches the differentiation program from visceral to parietal endoderm. Thus, unlike murine TC cells, in human NT2/D1 cells RA stimulates PKA-associated G proteins and PKA pathway activation enhances RA-mediated TC differentiation.
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PMID:Retinoic acid stimulates protein kinase A-associated G proteins during human teratocarcinoma differentiation. 818 70

Pertussis and cholera toxins failed to ADP-ribosylate G alpha s and G alpha i in membranes isolated from retinoic acid-differentiated HL-60 granulocytes, although G alpha i subunits were present. NAD was rapidly degraded in the presence of these membranes, primarily to ADP-ribose, to less than 10% of initial activity by 5 min. Metabolism of NAD was heat labile and inhibited by NADP, but not by imidazole or isonicotinic acid hydrazine. Pertussis toxin uncoupled LTB4 receptors from G proteins in intact retinoic acid-differentiated HL-60 cells. Retinoic acid differentiation stimulates expression of a unique NAD-glycohydrolase activity in HL-60 granulocytes which prevents ADP-ribosylation in isolated membranes, but not intact cells.
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PMID:Rapid degradation of NAD by retinoic acid-differentiated HL-60 granulocyte membranes prevents ADP ribosylation. 838 92

The effects of pertussis toxin, an uncoupler of Gi protein from adenylate cyclase, and luzindole, a competitive inhibitor of melatonin receptor binding, were examined for their ability to inhibit melatonin-induced suppression of PC12 cell growth. Both agents inhibited the melatonin response suggesting that melatonin may be acting through one of its Gi coupled cell surface receptors. This is confirmed by Western blots demonstrating the presence of MT1 receptors in PC12 cells. Coupling of the Gi protein to these receptors is demonstrated by failure of melatonin to suppress cell growth in PKA deficient A126-1B2-1 mutant PC12 cells. Similarly, melatonin failed to prevent cell proliferation when cells were incubated in the presence of the PKA inhibitor, Rp-cAMP. Retinoic acid and dexamethasone, agents known to effect PC12 cell growth and/or differentiation, displayed differential effects on the actions of melatonin. In the presence of melatonin and low concentrations of retinoic acid (100 nM), PC12 cell proliferation was stimulated compared to that seen with either agent alone, whereas no increase in cell proliferation was observed when higher concentrations of retinoic acid (100 microM) were used. The effects of dexamethasone on suppression of PC12 cell growth were additive with that of melatonin whereas, 1,25-dihydroxyvitamin D(3) (IC(50)=10 nM), which by itself had no effect on PC12 cell growth, was found to inhibit the melatonin response. This study demonstrates that inhibition of PC12 cell growth, at physiological concentrations of melatonin, is mediated by cAMP-dependent cell surface receptors and this response is altered by other growth factors known to effect PC12 cell proliferation and differentiation.
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PMID:Melatonin-induced suppression of PC12 cell growth is mediated by its Gi coupled transmembrane receptors. 1168 71