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Abstract:

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.

Registro:

Documento: Artículo
Título:Role of the DLL4-NOTCH system in PGF2alpha-induced luteolysis in the pregnant rat
Autor:Hernandez, F.; Peluffo, M.C.; Stouffer, R.L.; Irusta, G.; Tesone, M.
Filiación:Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina
Oregon National Primate Research Center, Oregon Health and Science University (ONPRC-OHSU), Beaverton, OR, United States
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave: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
Año:2011
Volumen:84
Número:5
Página de inicio:859
Página de fin:865
DOI: http://dx.doi.org/10.1095/biolreprod.110.088708
Título revista:Biology of Reproduction
Título revista abreviado:Biol. Reprod.
ISSN:00063363
CODEN:BIREB
CAS:caspase 3, 169592-56-7; progesterone, 57-83-0; prostaglandin F2 alpha, 551-11-1; protein bcl 2, 219306-68-0; Amyloid Precursor Protein Secretases, 3.4.-; Casp3 protein, rat, 3.4.22.-; Caspase 3, 3.4.22.-; Dinoprost, 551-11-1; Membrane Proteins; Notch1 protein, rat; Notch4 protein, rat; Peptide Fragments; Pregnancy Proteins; Progesterone, 57-83-0; Protease Inhibitors; RNA, Messenger; Receptor, Notch1; Receptors, Notch; delta protein
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00063363_v84_n5_p859_Hernandez

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Citas:

---------- APA ----------
Hernandez, F., Peluffo, M.C., Stouffer, R.L., Irusta, G. & Tesone, M. (2011) . Role of the DLL4-NOTCH system in PGF2alpha-induced luteolysis in the pregnant rat. Biology of Reproduction, 84(5), 859-865.
http://dx.doi.org/10.1095/biolreprod.110.088708
---------- CHICAGO ----------
Hernandez, F., Peluffo, M.C., Stouffer, R.L., Irusta, G., Tesone, M. "Role of the DLL4-NOTCH system in PGF2alpha-induced luteolysis in the pregnant rat" . Biology of Reproduction 84, no. 5 (2011) : 859-865.
http://dx.doi.org/10.1095/biolreprod.110.088708
---------- MLA ----------
Hernandez, F., Peluffo, M.C., Stouffer, R.L., Irusta, G., Tesone, M. "Role of the DLL4-NOTCH system in PGF2alpha-induced luteolysis in the pregnant rat" . Biology of Reproduction, vol. 84, no. 5, 2011, pp. 859-865.
http://dx.doi.org/10.1095/biolreprod.110.088708
---------- VANCOUVER ----------
Hernandez, F., Peluffo, M.C., Stouffer, R.L., Irusta, G., Tesone, M. Role of the DLL4-NOTCH system in PGF2alpha-induced luteolysis in the pregnant rat. Biol. Reprod. 2011;84(5):859-865.
http://dx.doi.org/10.1095/biolreprod.110.088708