Decrease in cAMP-dependent protein kinase activity in suspension cultures of porcine thyroid cells exposed to TSH or forskolin

Breton, Michelyne; Haye, Bernard; Omri, Boubaker; Jacquemin, Claude; Pavlović-Hournac, M.

doi:10.1016/0303-7207(88)90139-6

Cited by 15 publications

(6 citation statements)

References 39 publications

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“…Long exposure to PKA activating signals leads to either down‐ or up‐regulation of the catalytic subunit of PKA, depending on the cell type [31–36]. In attempt to shed more light on the role of PKA in controlling HTLV‐I gene expression we used the Jurkat cell line, in which long exposure to diBu‐cAMP severely down‐regulated PKA‐C, and H‐9 cell line, in which such exposure profoundly up‐regulated this catalytic subunit.…”

Section: Discussionmentioning

confidence: 99%

“…cAMP activates PKA by binding to its two regulatory subunits (PKA‐R) and dissociating, thereby, the two catalytic subunits (PKA‐C), which then migrate to the nucleus, where they phosphorylate the target transcription factors [29, 30]. Extended exposure to high intracellular cAMP level results in either up‐ [31, 32]or down‐regulation [33–36]of PKA‐C, depending on the cell type. In order to shed more light on the role of PKA in controlling HTLV‐I expression we decided to investigate the effect of this PKA‐C modulation on virus expression.…”

Section: Introductionmentioning

confidence: 99%

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Evidence that protein kinase A activity is required for the basal and tax‐stimulated transcriptional activity of human T‐cell leukemia virus type‐I long terminal repeat

Turgeman

Aboud

1998

FEBS Letters

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The present study was undertaken to investigate the role of protein kinase A (PKA) in the control of human T-cell leukemia virus type-I (HTLV-I) long terminal repeat (LTR) expression, since this issue is still controversial. For this purpose we employed two human T-cell lines; the Jurkat cells in which long exposure to diBu-cAMP severely down-regulated the catalytic subunit of PKA (PKA-C), and H-9 cells in which such exposure markedly increased PKA-C level. Transient transfection assays revealed that addition of diBu-cAMP 1 h before or after transfection profoundly increased HTLV-I LTR directed CAT expression and synergistically enhanced its stimulation by the viral transactivator tax gene product in both cell lines. However longer exposure to diBu-cAMP before transfection reduced LTR-CAT expression to below its basal level and completely abolished its stimulation by tax in Jurkat cells, and this diBu-cAMP inhibitory effect could be abrogated by cotransfection of a PKA-C expressing vector. By contrast, in H-9 cells, this long exposure to diBu-cAMP continued enhancing LTR-CAT expression and its tax-mediated transactivation, and this stimulatory effect of diBu-cAMP could be diminished by the PKA-specific inhibitor N-[2-(p-bromocinnamylamine)ethyl]-5-isoquinolinsulfonamide (H-89). Notably, in the absence of diBu-cAMP treatment H-89 reduced LTR-CAT expression to below its basal level and prevented its stimulation by tax in both cell lines. Together these findings indicate not only that cAMPactivated PKA stimulates HTLV-I LTR expression and its transactivation by tax, but even in the absence of PKA activating signals the basal HTLV-I LTR expression as well as its stimulation by tax are both dependent on a basal PKA activity.z 1998 Federation of European Biochemical Societies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evidence that protein kinase A activity is required for the basal and tax‐stimulated transcriptional activity of human T‐cell leukemia virus type‐I long terminal repeat

Turgeman

Aboud

1998

FEBS Letters

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“…TSH is also the most important stimulus to increase serum thyroglobulin levels and radioiodine uptake in normal, primary, and metastatic thyroid cancers of follicular cell origin [12][13][14]. Research investigations have also documented that normal and neoplastic thyroid tissue in humans and animals desensitized in response to repeated exposure of TSH [15][16][17][18]. There have also been a few reports documenting desensitization in neoplastic thyroid tissue [15].…”

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confidence: 99%

Desensitization in Normal and Neoplastic Human Thyroid Cell Lines

et al. 1998

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Abstract. Because some papillary thyroid cancers continue to grow when thyroid-stimulating hormone (TSH) levels are suppressed, we questioned whether desensitization (i.e., a decreased cAMP response to repeat stimulation with TSH) occurs in normal and neoplastic thyroid tissue. If desensitization does occur, is it similar or different in these human thyroid cells? Normal and papillary thyroid cancer cells from the same patient were cultured as we have previously described. Normal and neoplastic thyroid tissues responded to TSH (0.01-10.0 mU/ml) by increasing cAMP production and growth in a dose-dependent manner. In normal cells there was an 11-fold mean increase in cAMP production at 4 hours, and all thyroid cultures responded. In neoplastic cells cAMP production increased from 1.5-fold to 3.0-fold with a mean 2.0-fold increase at 4 hours. In normal thyroid cells the cAMP response to a second TSH stimulus (desensitization) decreased up to 75% (range 25-75%), and desensitization occurred in all normal thyroid cell cultures. In neoplastic thyroid cells, however, the cAMP response to a second TSH stimulus decreased up to 17% (range 0 -17%); and desensitization occurred in only two of the five neoplastic thyroid cell cultures. Thus when normal thyroid and neoplastic cells from the same patients were studied, greater desensitization occurred in the normal cells (75% vs. 17%). These studies document that there is greater desensitization in normal tissue than in neoplastic thyroid tissue, which may account for the increased growth of thyroid neoplasms in the presence of ever-changing low levels of TSH.

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“…TPA, however, reduced the cAMP response to TSH when both agonists were incubated in dog and pig thyroid cells [19 -21]. TSH decreased cAMP-dependent PKA activity in dog thyroid cells [22], but the simultaneous presence of TPA and TSH, in contrast, inhibited TSH-induced down-regulation of PKA I [19].…”

mentioning

confidence: 99%

Heterologous Desensitization in Neoplastic Thyroid Cells: Influence of the Phospholipase C Signal Transduction System on the Thyrotropin–adenylate Cyclase Signal Transduction System

Tezelman

Hoelting

Jossart³

et al. 1998

World j. surg.

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Desensitization is defined as a decreased functional response after continuous or repetitive stimulation of a receptor with its agonist. Thyrotropin (TSH) increases cAMP levels in normal and neoplastic thyroid tissue. The tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) activates protein kinase C (PKC). The aim was to determine whether TPA induces heterologous desensitization of the TSH-adenylate cyclase (AC) signal transduction system. Three human thyroid neoplasms in culture for 6 months or longer (one papillary carcinoma, one Hurthle cell carcinoma, one follicular adenoma) were incubated with TSH (10 mU/ml) and TPA (1.6 x 10(-8) M) separately and together for various time periods (from 10 minutes to 24 hours). The mixture was subsequently incubated for 30 minutes with TSH. TPA alone had no effect on cAMP levels, but co-incubation of TPA and TSH caused a significant reduction in cAMP response when compared to the cAMP response that resulted after stimulation with only TSH (p < 0.001). cAMP levels in response to TSH decreased by 31%, 44%, and 57% after preincubation with TSH for 10 minutes, 4 hours, and 24 hours, respectively (p < 0.01; ANOVA). Co-incubation of cells with TPA and staurosporine (10 ng/ml), a PKC inhibitor, prevented the effect of TPA on desensitization at 10 minutes and blunted the effect at 4 hours. This is the first demonstration in human neoplastic thyroid cells that TPA induced heterologous desensitization of the cAMP response to TSH. This TPA-induced effect appears to involve PKC activation, as it can be blocked by staurosporine.

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Decrease in cAMP-dependent protein kinase activity in suspension cultures of porcine thyroid cells exposed to TSH or forskolin

Cited by 15 publications

References 39 publications

Evidence that protein kinase A activity is required for the basal and tax‐stimulated transcriptional activity of human T‐cell leukemia virus type‐I long terminal repeat

Evidence that protein kinase A activity is required for the basal and tax‐stimulated transcriptional activity of human T‐cell leukemia virus type‐I long terminal repeat

Desensitization in Normal and Neoplastic Human Thyroid Cell Lines

Heterologous Desensitization in Neoplastic Thyroid Cells: Influence of the Phospholipase C Signal Transduction System on the Thyrotropin–adenylate Cyclase Signal Transduction System

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