Role of the DLL4-NOTCH system in PGF2alpha-induced luteolysis in the pregnant rat

We investigated the expression and cell localization of NOTCH1, NOTCH4, and the delta-like ligand DLL4 in corpus luteum (CL) from pregnant rats during prostaglandin F2alpha (PGF2alpha)-induced luteolysis. We also examined serum progesterone (P4) and CL proteins related to apoptosis after local admin...

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Autores principales:	Peluffo, Marina Cinthia, Irusta, Griselda, Tesone, Marta
Publicado:	2011
Materias:	Apoptosis Corpus luteum Ovary Pregnancy Progesterone/progesterone receptor caspase 3 delta like ligand DLL4 ligand messenger RNA n [n (3,5 difluorophenacetylalanyl)]phenylglycine tert butyl ester Notch1 receptor Notch4 receptor progesterone prostaglandin F2 alpha protein Bax protein bcl 2 protein inhibitor unclassified drug animal cell animal experiment animal tissue apoptosis article cell nucleus cell size cell viability controlled study corpus luteum cytoplasm enzyme activation female gene expression regulation luteolysis nonhuman pregnancy priority journal progesterone blood level protein cleavage protein degradation protein domain protein expression rat receptor binding signal transduction steroidogenesis Amyloid Precursor Protein Secretases Animals Caspase 3 Cell Nucleus Corpus Luteum Dinoprost Female Gene Expression Regulation Luteolysis Membrane Proteins Peptide Fragments Pregnancy Proteins Progesterone Protease Inhibitors Rats Rats, Sprague-Dawley Receptor, Notch1 Receptors, Notch RNA, Messenger Signal Transduction Rattus
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00063363_v84_n5_p859_Hernandez http://hdl.handle.net/20.500.12110/paper_00063363_v84_n5_p859_Hernandez
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paper:paper_00063363_v84_n5_p859_Hernandez2023-06-08T14:31:09Z Role of the DLL4-NOTCH system in PGF2alpha-induced luteolysis in the pregnant rat Peluffo, Marina Cinthia Irusta, Griselda Tesone, Marta Apoptosis Corpus luteum Ovary Pregnancy Progesterone/progesterone receptor caspase 3 delta like ligand DLL4 ligand messenger RNA n [n (3,5 difluorophenacetylalanyl)]phenylglycine tert butyl ester Notch1 receptor Notch4 receptor progesterone prostaglandin F2 alpha protein Bax protein bcl 2 protein inhibitor unclassified drug animal cell animal experiment animal tissue apoptosis article cell nucleus cell size cell viability controlled study corpus luteum cytoplasm enzyme activation female gene expression regulation luteolysis nonhuman pregnancy priority journal progesterone blood level protein cleavage protein degradation protein domain protein expression rat receptor binding signal transduction steroidogenesis Amyloid Precursor Protein Secretases Animals Apoptosis Caspase 3 Cell Nucleus Corpus Luteum Dinoprost Female Gene Expression Regulation Luteolysis Membrane Proteins Peptide Fragments Pregnancy Pregnancy Proteins Progesterone Protease Inhibitors Rats Rats, Sprague-Dawley Receptor, Notch1 Receptors, Notch RNA, Messenger Signal Transduction Rattus We investigated the expression and cell localization of NOTCH1, NOTCH4, and the delta-like ligand DLL4 in corpus luteum (CL) from pregnant rats during prostaglandin F2alpha (PGF2alpha)-induced luteolysis. We also examined serum progesterone (P4) and CL proteins related to apoptosis after local administration of the notch inhibitor N-[N-(3,5-difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester (DAPT). Specific staining for NOTCH1 and NOTCH4 receptors was detected predominantly in large and small luteal cells. Furthermore, in line with the fact that the notch intracellular domain is translocated to the nucleus, where it regulates gene expression, staining was evident in the nuclei of luteal cells. In addition, we detected diffuse cytoplasmic immunostaining for DLL4 in small and large luteal cells, in accordance with the fact that DLL4 undergoes proteolytic degradation after receptor binding. The mRNA expression of Notch1, Notch4, and Dll4 in CL isolated on Day 19 of pregnancy decreased significantly after administration of PGF2alpha. Consistent with the mRNA results, administration of PGF2alpha to pregnant rats on Day 19 of pregnancy decreased the protein fragment corresponding to the cleaved forms of NOTCH1/4 CL receptors. In contrast, no significant changes were detected in protein levels for the ligand DLL4. The local intrabursal administration of DAPT decreased serum P4 levels and increased luteal levels of active caspase 3 and the BAX:BCL2 ratio 24 h after the treatment. These results support a luteotropic role for notch signaling to promote luteal cell viability and steroidogenesis, and they suggest that the luteolytic hormone PGF2alpha may act in part by reducing the expression of some notch system members. © 2011 by the Society for the Study of Reproduction, Inc. Fil:Peluffo, M.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Irusta, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Tesone, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2011 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00063363_v84_n5_p859_Hernandez http://hdl.handle.net/20.500.12110/paper_00063363_v84_n5_p859_Hernandez
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Apoptosis Corpus luteum Ovary Pregnancy Progesterone/progesterone receptor caspase 3 delta like ligand DLL4 ligand messenger RNA n [n (3,5 difluorophenacetylalanyl)]phenylglycine tert butyl ester Notch1 receptor Notch4 receptor progesterone prostaglandin F2 alpha protein Bax protein bcl 2 protein inhibitor unclassified drug animal cell animal experiment animal tissue apoptosis article cell nucleus cell size cell viability controlled study corpus luteum cytoplasm enzyme activation female gene expression regulation luteolysis nonhuman pregnancy priority journal progesterone blood level protein cleavage protein degradation protein domain protein expression rat receptor binding signal transduction steroidogenesis Amyloid Precursor Protein Secretases Animals Apoptosis Caspase 3 Cell Nucleus Corpus Luteum Dinoprost Female Gene Expression Regulation Luteolysis Membrane Proteins Peptide Fragments Pregnancy Pregnancy Proteins Progesterone Protease Inhibitors Rats Rats, Sprague-Dawley Receptor, Notch1 Receptors, Notch RNA, Messenger Signal Transduction Rattus
spellingShingle	Apoptosis Corpus luteum Ovary Pregnancy Progesterone/progesterone receptor caspase 3 delta like ligand DLL4 ligand messenger RNA n [n (3,5 difluorophenacetylalanyl)]phenylglycine tert butyl ester Notch1 receptor Notch4 receptor progesterone prostaglandin F2 alpha protein Bax protein bcl 2 protein inhibitor unclassified drug animal cell animal experiment animal tissue apoptosis article cell nucleus cell size cell viability controlled study corpus luteum cytoplasm enzyme activation female gene expression regulation luteolysis nonhuman pregnancy priority journal progesterone blood level protein cleavage protein degradation protein domain protein expression rat receptor binding signal transduction steroidogenesis Amyloid Precursor Protein Secretases Animals Apoptosis Caspase 3 Cell Nucleus Corpus Luteum Dinoprost Female Gene Expression Regulation Luteolysis Membrane Proteins Peptide Fragments Pregnancy Pregnancy Proteins Progesterone Protease Inhibitors Rats Rats, Sprague-Dawley Receptor, Notch1 Receptors, Notch RNA, Messenger Signal Transduction Rattus Peluffo, Marina Cinthia Irusta, Griselda Tesone, Marta Role of the DLL4-NOTCH system in PGF2alpha-induced luteolysis in the pregnant rat
topic_facet	Apoptosis Corpus luteum Ovary Pregnancy Progesterone/progesterone receptor caspase 3 delta like ligand DLL4 ligand messenger RNA n [n (3,5 difluorophenacetylalanyl)]phenylglycine tert butyl ester Notch1 receptor Notch4 receptor progesterone prostaglandin F2 alpha protein Bax protein bcl 2 protein inhibitor unclassified drug animal cell animal experiment animal tissue apoptosis article cell nucleus cell size cell viability controlled study corpus luteum cytoplasm enzyme activation female gene expression regulation luteolysis nonhuman pregnancy priority journal progesterone blood level protein cleavage protein degradation protein domain protein expression rat receptor binding signal transduction steroidogenesis Amyloid Precursor Protein Secretases Animals Apoptosis Caspase 3 Cell Nucleus Corpus Luteum Dinoprost Female Gene Expression Regulation Luteolysis Membrane Proteins Peptide Fragments Pregnancy Pregnancy Proteins Progesterone Protease Inhibitors Rats Rats, Sprague-Dawley Receptor, Notch1 Receptors, Notch RNA, Messenger Signal Transduction Rattus
description	We investigated the expression and cell localization of NOTCH1, NOTCH4, and the delta-like ligand DLL4 in corpus luteum (CL) from pregnant rats during prostaglandin F2alpha (PGF2alpha)-induced luteolysis. We also examined serum progesterone (P4) and CL proteins related to apoptosis after local administration of the notch inhibitor N-[N-(3,5-difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester (DAPT). Specific staining for NOTCH1 and NOTCH4 receptors was detected predominantly in large and small luteal cells. Furthermore, in line with the fact that the notch intracellular domain is translocated to the nucleus, where it regulates gene expression, staining was evident in the nuclei of luteal cells. In addition, we detected diffuse cytoplasmic immunostaining for DLL4 in small and large luteal cells, in accordance with the fact that DLL4 undergoes proteolytic degradation after receptor binding. The mRNA expression of Notch1, Notch4, and Dll4 in CL isolated on Day 19 of pregnancy decreased significantly after administration of PGF2alpha. Consistent with the mRNA results, administration of PGF2alpha to pregnant rats on Day 19 of pregnancy decreased the protein fragment corresponding to the cleaved forms of NOTCH1/4 CL receptors. In contrast, no significant changes were detected in protein levels for the ligand DLL4. The local intrabursal administration of DAPT decreased serum P4 levels and increased luteal levels of active caspase 3 and the BAX:BCL2 ratio 24 h after the treatment. These results support a luteotropic role for notch signaling to promote luteal cell viability and steroidogenesis, and they suggest that the luteolytic hormone PGF2alpha may act in part by reducing the expression of some notch system members. © 2011 by the Society for the Study of Reproduction, Inc.
author	Peluffo, Marina Cinthia Irusta, Griselda Tesone, Marta
author_facet	Peluffo, Marina Cinthia Irusta, Griselda Tesone, Marta
author_sort	Peluffo, Marina Cinthia
title	Role of the DLL4-NOTCH system in PGF2alpha-induced luteolysis in the pregnant rat
title_short	Role of the DLL4-NOTCH system in PGF2alpha-induced luteolysis in the pregnant rat
title_full	Role of the DLL4-NOTCH system in PGF2alpha-induced luteolysis in the pregnant rat
title_fullStr	Role of the DLL4-NOTCH system in PGF2alpha-induced luteolysis in the pregnant rat
title_full_unstemmed	Role of the DLL4-NOTCH system in PGF2alpha-induced luteolysis in the pregnant rat
title_sort	role of the dll4-notch system in pgf2alpha-induced luteolysis in the pregnant rat
publishDate	2011
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00063363_v84_n5_p859_Hernandez http://hdl.handle.net/20.500.12110/paper_00063363_v84_n5_p859_Hernandez
work_keys_str_mv	AT peluffomarinacinthia roleofthedll4notchsysteminpgf2alphainducedluteolysisinthepregnantrat AT irustagriselda roleofthedll4notchsysteminpgf2alphainducedluteolysisinthepregnantrat AT tesonemarta roleofthedll4notchsysteminpgf2alphainducedluteolysisinthepregnantrat
_version_	1768543590093422592

Role of the DLL4-NOTCH system in PGF2alpha-induced luteolysis in the pregnant rat

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