Search PubMed⌕ Search

Biomedical subjects

T Kino

Publications and source records attributed to T Kino.

96 records · Page 6Linked to original sources
PubMedDate not supplied

Conditional modulation of glucocorticoid receptor activities by CREB-binding protein (CBP) and p300.

Coactivators of nuclear receptors are integral components of the signal transduction pathways of steroid hormones. Here, we show that one of the major coactivators of the glucocorticoid receptor (GR), CREB-binding protein (CBP), can also function conditionally as a negative regulator of its activities. Indeed, CBP suppressed the responsiveness of the mouse mammary tumor virus (MMTV) promoter to dexamethasone in a dose-dependent fashion in HeLa and A204 cells. Similarly, this protein suppressed the responsiveness of several glucocorticoid-responsive element (GRE)-containing synthetic promoters. Using deletion mutants of CBP, we localized the repressor effect of this protein to its N-terminal domain and showed that it was independent of the histone acetyltransferase and coactivator-binding domains but dependent upon its GR-binding domain. We also demonstrated functional differentiation between CBP and other coactivators, including SRC-1 and the CBP-related protein p300, both of which influenced GR signaling in a positive fashion. In fact, p300 completely antagonized the suppressive effects of CBP in a dose-dependent fashion, probably by competing with this protein at the level of the transcription complex. These findings suggest that CBP and p300 may function additively or antagonistically to each other depending on their relative concentrations and type of target tissue, to influence the sensitivity of tissues to glucocorticoids.

Animals↗
PubMedDate not supplied

Basal catecholamine and cortisol secretion in primary chromaffin cell cultures before and after purification and retroviral transfection.

We have investigated the effects of supraphysiological concentrations of catecholamines on glucocorticoid secretion in vitro. These effects were analyzed in adrenocortical cells shown to be present in chromaffin cell cultures as well as in cortical cells cocultured with transfected chromaffin cells that overproduce catecholamines. Cortisol release from residual cortical cells in chromaffin cell cultures was found to be 2.5 times higher than from isolated adrenocortical cells. Removal of the adrenocortical cells from the chromaffin cells resulted in an almost complete cessation of cortisol secretion. Catecholamine overproduction was achieved by transfecting chromaffin cells with the blank retroviral vector pSAM-EN. Coculture of adrenocortical cells with these transfected chromaffin cells further enhanced the stimulating effect of chromaffin cells on cortisol 2.3-fold compared to normal cocultures. In conclusion, cortical cells in chromaffin cell cultures secrete significant amounts of cortisol, which should be considered when evaluating the endocrine function of these cell cultures and which can be abolished by purification. The hormonal activity of adrenocortical cells is highly increased in an environment of catecholamine overproduction, which is of both basic and clinical importance.

Adrenal Cortex↗
PubMedDate not supplied

Increased releasability of platelet products and reduced heparin-induced platelet factor 4 release from endothelial cells in bronchial asthma.

To determine whether or not platelet activation is involved in the mechanism of exacerbation of bronchial asthma, we evaluated adenosine triphosphate (ATP) release from thrombin-stimulated washed platelets, plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4), and plasma beta-TG/PF4 ratios during symptomatic and asymptomatic periods in 15 patients with bronchial asthma compared with 16 normal control subjects. We also measured these parameters during allergen provocation tests and acetylcholine inhalation tests in 6 allergic asthmatics. ATP release, plasma levels of beta-TG and PF4 were significantly increased during symptomatic periods and after the allergen provocations but not after acetylcholine inhalations. However, these findings were not accompanied by the elevation of plasma beta-TG/PF4 ratios. The heparin-induced PF4 release, which is reported to reflect release of PF4 attached on endothelial cells, was significantly reduced in 12 asymptomatic asthmatic patients compared with 11 normal subjects, and it was much more reduced in 7 symptomatic asthmatic patients, suggesting the possibility of the reduced PF4 binding on endothelial cell surface. This finding may represent the prolonged half life of PF4 in asthmatics. We concluded that 1) increased releasability of platelet products and in vivo release of the platelet granular contents are involved in the mechanism of the exacerbation of bronchial asthma, 2) some functional alteration in platelet-endothelial cell interaction may be involved in bronchial asthma, and 3) plasma beta-TG/PF4 ratios are not elevated possibly because of both increased platelet releasability and prolonged half-life of PF4 in the blood in asthmatic patients.

Acetylcholine↗