Endocannabinoids participate in placental apoptosis induced by hypoxia inducible factor-1

During pregnancy, apoptosis is a physiological event critical in the remodeling and aging of the placenta. Increasing evidence has pointed towards the relevance of endocannabinoids (ECs) and hypoxia as modulators of trophoblast cell death. However, the relation between these factors is still unknown...

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Autores principales:	Franchi, Ana María, Farina, Mariana
Publicado:	2016
Materias:	Apoptosis Endocannabinoids Hipoxia inducible factor 1 Placenta cannabinoid 1 receptor caspase 3 chorionic gonadotropin beta subunit endocannabinoid fatty acid amidase hypoxia inducible factor 1 lactate dehydrogenase messenger RNA nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase protein Bax protein bcl 2 BCL2 protein, human CASP3 protein, human cobalt cobalt chloride hypoxia inducible factor 1alpha apoptosis Article cell viability controlled study enzyme activation female hormone synthesis human human tissue hypoxia immunoreactivity intracellular signaling placenta placenta tissue priority journal protein cleavage protein expression protein induction protein localization protein stability syncytiotrophoblast upregulation cell hypoxia cell survival cytology drug effects genetics metabolism pregnancy signal transduction Caspase 3 Cell Hypoxia Cell Survival Cobalt Female Humans Hypoxia-Inducible Factor 1, alpha Subunit Pregnancy Proto-Oncogene Proteins c-bcl-2 Signal Transduction
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13608185_v21_n10_p1094_Aban http://hdl.handle.net/20.500.12110/paper_13608185_v21_n10_p1094_Aban
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_13608185_v21_n10_p1094_Aban
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spelling	paper:paper_13608185_v21_n10_p1094_Aban2023-06-08T16:11:34Z Endocannabinoids participate in placental apoptosis induced by hypoxia inducible factor-1 Franchi, Ana María Farina, Mariana Apoptosis Endocannabinoids Hipoxia inducible factor 1 Placenta cannabinoid 1 receptor caspase 3 chorionic gonadotropin beta subunit endocannabinoid fatty acid amidase hypoxia inducible factor 1 lactate dehydrogenase messenger RNA nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase protein Bax protein bcl 2 BCL2 protein, human CASP3 protein, human caspase 3 cobalt cobalt chloride endocannabinoid hypoxia inducible factor 1alpha protein bcl 2 apoptosis Article cell viability controlled study enzyme activation female hormone synthesis human human tissue hypoxia immunoreactivity intracellular signaling placenta placenta tissue priority journal protein cleavage protein expression protein induction protein localization protein stability syncytiotrophoblast upregulation cell hypoxia cell survival cytology drug effects genetics metabolism placenta pregnancy signal transduction Apoptosis Caspase 3 Cell Hypoxia Cell Survival Cobalt Endocannabinoids Female Humans Hypoxia-Inducible Factor 1, alpha Subunit Placenta Pregnancy Proto-Oncogene Proteins c-bcl-2 Signal Transduction During pregnancy, apoptosis is a physiological event critical in the remodeling and aging of the placenta. Increasing evidence has pointed towards the relevance of endocannabinoids (ECs) and hypoxia as modulators of trophoblast cell death. However, the relation between these factors is still unknown. In this report, we evaluated the participation of ECs in placental apoptosis induced by cobalt chloride (CoCl2), a hypoxia mimicking agent that stabilizes the expression of hypoxia inducible factor-1 alpha (HIF-1α). We found that HIF-1α stabilization decreased FAAH mRNA and protein levels, suggesting an increase in ECs tone. Additionally, CoCl2 incubation and Met-AEA treatment reduced cell viability and increased TUNEL-positive staining in syncytiotrophoblast layer. Immunohistochemical analysis demonstrated Bax and Bcl-2 protein expression in the cytoplasm of syncytiotrophoblast. Finally, HIF-1α stabilization produced an increase in Bax/Bcl-2 ratio, activation of caspase 3 and PARP cleavage. All these changes in apoptotic parameters were reversed with AM251, a CB1 antagonist. These results demonstrate that HIF-1α may induce apoptosis in human placenta via intrinsic pathway by a mechanism that involves activation of CB1 receptor suggesting a role of the ECs in this process. © 2016, Springer Science+Business Media New York. Fil:Franchi, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Farina, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13608185_v21_n10_p1094_Aban http://hdl.handle.net/20.500.12110/paper_13608185_v21_n10_p1094_Aban
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 Endocannabinoids Hipoxia inducible factor 1 Placenta cannabinoid 1 receptor caspase 3 chorionic gonadotropin beta subunit endocannabinoid fatty acid amidase hypoxia inducible factor 1 lactate dehydrogenase messenger RNA nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase protein Bax protein bcl 2 BCL2 protein, human CASP3 protein, human caspase 3 cobalt cobalt chloride endocannabinoid hypoxia inducible factor 1alpha protein bcl 2 apoptosis Article cell viability controlled study enzyme activation female hormone synthesis human human tissue hypoxia immunoreactivity intracellular signaling placenta placenta tissue priority journal protein cleavage protein expression protein induction protein localization protein stability syncytiotrophoblast upregulation cell hypoxia cell survival cytology drug effects genetics metabolism placenta pregnancy signal transduction Apoptosis Caspase 3 Cell Hypoxia Cell Survival Cobalt Endocannabinoids Female Humans Hypoxia-Inducible Factor 1, alpha Subunit Placenta Pregnancy Proto-Oncogene Proteins c-bcl-2 Signal Transduction
spellingShingle	Apoptosis Endocannabinoids Hipoxia inducible factor 1 Placenta cannabinoid 1 receptor caspase 3 chorionic gonadotropin beta subunit endocannabinoid fatty acid amidase hypoxia inducible factor 1 lactate dehydrogenase messenger RNA nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase protein Bax protein bcl 2 BCL2 protein, human CASP3 protein, human caspase 3 cobalt cobalt chloride endocannabinoid hypoxia inducible factor 1alpha protein bcl 2 apoptosis Article cell viability controlled study enzyme activation female hormone synthesis human human tissue hypoxia immunoreactivity intracellular signaling placenta placenta tissue priority journal protein cleavage protein expression protein induction protein localization protein stability syncytiotrophoblast upregulation cell hypoxia cell survival cytology drug effects genetics metabolism placenta pregnancy signal transduction Apoptosis Caspase 3 Cell Hypoxia Cell Survival Cobalt Endocannabinoids Female Humans Hypoxia-Inducible Factor 1, alpha Subunit Placenta Pregnancy Proto-Oncogene Proteins c-bcl-2 Signal Transduction Franchi, Ana María Farina, Mariana Endocannabinoids participate in placental apoptosis induced by hypoxia inducible factor-1
topic_facet	Apoptosis Endocannabinoids Hipoxia inducible factor 1 Placenta cannabinoid 1 receptor caspase 3 chorionic gonadotropin beta subunit endocannabinoid fatty acid amidase hypoxia inducible factor 1 lactate dehydrogenase messenger RNA nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase protein Bax protein bcl 2 BCL2 protein, human CASP3 protein, human caspase 3 cobalt cobalt chloride endocannabinoid hypoxia inducible factor 1alpha protein bcl 2 apoptosis Article cell viability controlled study enzyme activation female hormone synthesis human human tissue hypoxia immunoreactivity intracellular signaling placenta placenta tissue priority journal protein cleavage protein expression protein induction protein localization protein stability syncytiotrophoblast upregulation cell hypoxia cell survival cytology drug effects genetics metabolism placenta pregnancy signal transduction Apoptosis Caspase 3 Cell Hypoxia Cell Survival Cobalt Endocannabinoids Female Humans Hypoxia-Inducible Factor 1, alpha Subunit Placenta Pregnancy Proto-Oncogene Proteins c-bcl-2 Signal Transduction
description	During pregnancy, apoptosis is a physiological event critical in the remodeling and aging of the placenta. Increasing evidence has pointed towards the relevance of endocannabinoids (ECs) and hypoxia as modulators of trophoblast cell death. However, the relation between these factors is still unknown. In this report, we evaluated the participation of ECs in placental apoptosis induced by cobalt chloride (CoCl2), a hypoxia mimicking agent that stabilizes the expression of hypoxia inducible factor-1 alpha (HIF-1α). We found that HIF-1α stabilization decreased FAAH mRNA and protein levels, suggesting an increase in ECs tone. Additionally, CoCl2 incubation and Met-AEA treatment reduced cell viability and increased TUNEL-positive staining in syncytiotrophoblast layer. Immunohistochemical analysis demonstrated Bax and Bcl-2 protein expression in the cytoplasm of syncytiotrophoblast. Finally, HIF-1α stabilization produced an increase in Bax/Bcl-2 ratio, activation of caspase 3 and PARP cleavage. All these changes in apoptotic parameters were reversed with AM251, a CB1 antagonist. These results demonstrate that HIF-1α may induce apoptosis in human placenta via intrinsic pathway by a mechanism that involves activation of CB1 receptor suggesting a role of the ECs in this process. © 2016, Springer Science+Business Media New York.
author	Franchi, Ana María Farina, Mariana
author_facet	Franchi, Ana María Farina, Mariana
author_sort	Franchi, Ana María
title	Endocannabinoids participate in placental apoptosis induced by hypoxia inducible factor-1
title_short	Endocannabinoids participate in placental apoptosis induced by hypoxia inducible factor-1
title_full	Endocannabinoids participate in placental apoptosis induced by hypoxia inducible factor-1
title_fullStr	Endocannabinoids participate in placental apoptosis induced by hypoxia inducible factor-1
title_full_unstemmed	Endocannabinoids participate in placental apoptosis induced by hypoxia inducible factor-1
title_sort	endocannabinoids participate in placental apoptosis induced by hypoxia inducible factor-1
publishDate	2016
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13608185_v21_n10_p1094_Aban http://hdl.handle.net/20.500.12110/paper_13608185_v21_n10_p1094_Aban
work_keys_str_mv	AT franchianamaria endocannabinoidsparticipateinplacentalapoptosisinducedbyhypoxiainduciblefactor1 AT farinamariana endocannabinoidsparticipateinplacentalapoptosisinducedbyhypoxiainduciblefactor1
_version_	1768546035232145408

Endocannabinoids participate in placental apoptosis induced by hypoxia inducible factor-1

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