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Signal transduction pathways underlying the expression of tissue factor and thrombomodulin in promyelocytic cells induced to differentiate by retinoid acid and dibutyryl cAMP.
Thromb Haemost. 2001 Jun; 85(6):1031-6.TH

Abstract

Acute promyelocytic leukaemia (APL) may be associated with disseminated intravascular coagulation, as a result of increased tissue factor (TF) expression and reduced thrombomodulin (TM) expression by APL blast cells. During retinoid acid (RA)- and dibutyryl cAMP (dbcAMP)-induced differentiation of the APL cells, there is a marked up-modulation of both the protein kinase A (PKA) and C (PKC) activities. In order to further assess whether these kinases are intimately associated with both the differentiation process and the regulation of TF and TM expression, we have correlated the modulation of their respective pathways with the extent of differentiation and modulation of these cellular receptors. NB4 cells were incubated with all-trans-RA (ATRA) or dbcAMP for up to 48 h. The contribution of phospholipase C (PLC), inositol phosphate (IP), PKC and PKA in the expression of CD11b, TF and TM was studied by the use of specific inhibitors. Myo-inositol uptake and PKC activity increased in cells induced to differentiate by ATRA but the retinoid did not affect cAMP levels or PKA activity. Under treatment with dbcAMP, PKA activity was increased while inositol uptake and PKC activity remained unchanged. Our results show that the effects of ATRA and dbcAMP on promyelocytic cells are closely related, respectively, to the PLC/IP/PKC and the cAMP/PKA pathways. In cells induced to differentiate by ATRA, CD11b expression seems more closely related to inositol uptake than to PKC activity while the expression of TF and TM show the opposite pattern, which suggests cellular events regulated at a different level within a common signal transduction pathway.

Authors+Show Affiliations

Department of Research, Reina Sofia University Hopsital, Cordoba, Spain. pmdb@sofia.hrs.sas.cica.esNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11434680

Citation

López-Pedrera, C, et al. "Signal Transduction Pathways Underlying the Expression of Tissue Factor and Thrombomodulin in Promyelocytic Cells Induced to Differentiate By Retinoid Acid and Dibutyryl CAMP." Thrombosis and Haemostasis, vol. 85, no. 6, 2001, pp. 1031-6.
López-Pedrera C, Dobado-Berrios PM, Ros R, et al. Signal transduction pathways underlying the expression of tissue factor and thrombomodulin in promyelocytic cells induced to differentiate by retinoid acid and dibutyryl cAMP. Thromb Haemost. 2001;85(6):1031-6.
López-Pedrera, C., Dobado-Berrios, P. M., Ros, R., Torres, A., García-Navarro, S., Jardí, M., Félez, J., & Velasco, F. (2001). Signal transduction pathways underlying the expression of tissue factor and thrombomodulin in promyelocytic cells induced to differentiate by retinoid acid and dibutyryl cAMP. Thrombosis and Haemostasis, 85(6), 1031-6.
López-Pedrera C, et al. Signal Transduction Pathways Underlying the Expression of Tissue Factor and Thrombomodulin in Promyelocytic Cells Induced to Differentiate By Retinoid Acid and Dibutyryl CAMP. Thromb Haemost. 2001;85(6):1031-6. PubMed PMID: 11434680.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Signal transduction pathways underlying the expression of tissue factor and thrombomodulin in promyelocytic cells induced to differentiate by retinoid acid and dibutyryl cAMP. AU - López-Pedrera,C, AU - Dobado-Berrios,P M, AU - Ros,R, AU - Torres,A, AU - García-Navarro,S, AU - Jardí,M, AU - Félez,J, AU - Velasco,F, PY - 2001/7/4/pubmed PY - 2002/7/12/medline PY - 2001/7/4/entrez SP - 1031 EP - 6 JF - Thrombosis and haemostasis JO - Thromb Haemost VL - 85 IS - 6 N2 - Acute promyelocytic leukaemia (APL) may be associated with disseminated intravascular coagulation, as a result of increased tissue factor (TF) expression and reduced thrombomodulin (TM) expression by APL blast cells. During retinoid acid (RA)- and dibutyryl cAMP (dbcAMP)-induced differentiation of the APL cells, there is a marked up-modulation of both the protein kinase A (PKA) and C (PKC) activities. In order to further assess whether these kinases are intimately associated with both the differentiation process and the regulation of TF and TM expression, we have correlated the modulation of their respective pathways with the extent of differentiation and modulation of these cellular receptors. NB4 cells were incubated with all-trans-RA (ATRA) or dbcAMP for up to 48 h. The contribution of phospholipase C (PLC), inositol phosphate (IP), PKC and PKA in the expression of CD11b, TF and TM was studied by the use of specific inhibitors. Myo-inositol uptake and PKC activity increased in cells induced to differentiate by ATRA but the retinoid did not affect cAMP levels or PKA activity. Under treatment with dbcAMP, PKA activity was increased while inositol uptake and PKC activity remained unchanged. Our results show that the effects of ATRA and dbcAMP on promyelocytic cells are closely related, respectively, to the PLC/IP/PKC and the cAMP/PKA pathways. In cells induced to differentiate by ATRA, CD11b expression seems more closely related to inositol uptake than to PKC activity while the expression of TF and TM show the opposite pattern, which suggests cellular events regulated at a different level within a common signal transduction pathway. SN - 0340-6245 UR - https://www.unboundmedicine.com/medline/citation/11434680/Signal_transduction_pathways_underlying_the_expression_of_tissue_factor_and_thrombomodulin_in_promyelocytic_cells_induced_to_differentiate_by_retinoid_acid_and_dibutyryl_cAMP_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=11434680.ui DB - PRIME DP - Unbound Medicine ER -