Involvement of PI3K/Akt and p38 MAPK in the induction of COX-2 expression by bacterial lipopolysaccharide in murine adrenocortical cells

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Previous studies from our laboratory demonstrated the involvement of COX-2 in the stimulation of steroid production by LPS in murine adrenocortical Y1 cells, as well as in the adrenal cortex of male Wistar rats. In this paper we analyzed signaling pathways involved in the induction of this key regul...

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Autores principales:	Mercau, M.E., Astort, F., Giordanino, E.F., Martinez Calejman, C., Sanchez, R., Caldareri, L., Repetto, E.M., Coso, O.A., Cymeryng, C.B.
Formato:	JOUR
Materias:	Adrenocortical cells AKT/PKB Cyclooxygenase-2 Lipopolysaccharide P38 MAPK 2 morpholino 8 phenylchromone bacterium lipopolysaccharide cyclooxygenase 2 immunoglobulin enhancer binding protein messenger RNA mitogen activated protein kinase p38 phosphatidylinositol 3 kinase protein kinase B reactive oxygen metabolite adrenal cortex cell animal cell article controlled study enzyme activity enzyme induction enzyme inhibition enzyme phosphorylation mouse nonhuman priority journal protein expression rat signal transduction p38 MAPK Adrenal Cortex Animals Antioxidants Cell Line, Tumor Chromones Cyclooxygenase 2 Enzyme Inhibitors Gene Expression Regulation Lipopolysaccharides Male Mice Morpholines p38 Mitogen-Activated Protein Kinases Phosphatidylinositol 3-Kinases Phosphorylation Primary Cell Culture Proto-Oncogene Proteins c-akt Rats Reactive Oxygen Species Signal Transduction
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_03037207_v384_n1-2_p43_Mercau
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_03037207_v384_n1-2_p43_Mercau2023-10-03T15:19:57Z Involvement of PI3K/Akt and p38 MAPK in the induction of COX-2 expression by bacterial lipopolysaccharide in murine adrenocortical cells Mercau, M.E. Astort, F. Giordanino, E.F. Martinez Calejman, C. Sanchez, R. Caldareri, L. Repetto, E.M. Coso, O.A. Cymeryng, C.B. Adrenocortical cells AKT/PKB Cyclooxygenase-2 Lipopolysaccharide P38 MAPK 2 morpholino 8 phenylchromone bacterium lipopolysaccharide cyclooxygenase 2 immunoglobulin enhancer binding protein messenger RNA mitogen activated protein kinase p38 phosphatidylinositol 3 kinase protein kinase B reactive oxygen metabolite adrenal cortex cell animal cell article controlled study enzyme activity enzyme induction enzyme inhibition enzyme phosphorylation mouse nonhuman priority journal protein expression rat signal transduction Adrenocortical cells AKT/PKB Cyclooxygenase-2 Lipopolysaccharide p38 MAPK Adrenal Cortex Animals Antioxidants Cell Line, Tumor Chromones Cyclooxygenase 2 Enzyme Inhibitors Gene Expression Regulation Lipopolysaccharides Male Mice Morpholines p38 Mitogen-Activated Protein Kinases Phosphatidylinositol 3-Kinases Phosphorylation Primary Cell Culture Proto-Oncogene Proteins c-akt Rats Reactive Oxygen Species Signal Transduction Previous studies from our laboratory demonstrated the involvement of COX-2 in the stimulation of steroid production by LPS in murine adrenocortical Y1 cells, as well as in the adrenal cortex of male Wistar rats. In this paper we analyzed signaling pathways involved in the induction of this key regulatory enzyme in adrenocortical cells and demonstrated that LPS triggers an increase in COX-2 mRNA levels by mechanisms involving the stimulation of reactive oxygen species (ROS) generation and the activation of p38 MAPK and Akt, in addition to the previously demonstrated increase in NFκB activity. In this sense we showed that: (1) inhibition of p38 MAPK or PI3K/Akt (pharmacological or molecular) prevented the increase in COX-2 protein levels by LPS, (2) LPS induced p38 MAPK and Akt phosphorylation, (3) antioxidant treatment blocked the effect of LPS on p38 MAPK phosphorylation and in COX-2 protein levels, (4) PI3K inhibition with LY294002 prevented p38 MAPK phosphorylation and, (5) the activity of an NFκB reporter was decreased by p38 MAPK or PI3K inhibition.These results suggest that activation of both p38 MAPK and PI3K/Akt pathways promote the stimulation of NFκB activity and that PI3K/Akt activity might regulate both p38 MAPK and NFκB signaling pathways.In summary, in this study we showed that in adrenal cells, LPS induces COX-2 expression by activating p38 MAPK and PI3K/Akt signaling pathways and that both pathways converge in the modulation of NFκB transcriptional activity. © 2014 Elsevier Ireland Ltd. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_03037207_v384_n1-2_p43_Mercau
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Adrenocortical cells AKT/PKB Cyclooxygenase-2 Lipopolysaccharide P38 MAPK 2 morpholino 8 phenylchromone bacterium lipopolysaccharide cyclooxygenase 2 immunoglobulin enhancer binding protein messenger RNA mitogen activated protein kinase p38 phosphatidylinositol 3 kinase protein kinase B reactive oxygen metabolite adrenal cortex cell animal cell article controlled study enzyme activity enzyme induction enzyme inhibition enzyme phosphorylation mouse nonhuman priority journal protein expression rat signal transduction Adrenocortical cells AKT/PKB Cyclooxygenase-2 Lipopolysaccharide p38 MAPK Adrenal Cortex Animals Antioxidants Cell Line, Tumor Chromones Cyclooxygenase 2 Enzyme Inhibitors Gene Expression Regulation Lipopolysaccharides Male Mice Morpholines p38 Mitogen-Activated Protein Kinases Phosphatidylinositol 3-Kinases Phosphorylation Primary Cell Culture Proto-Oncogene Proteins c-akt Rats Reactive Oxygen Species Signal Transduction
spellingShingle	Adrenocortical cells AKT/PKB Cyclooxygenase-2 Lipopolysaccharide P38 MAPK 2 morpholino 8 phenylchromone bacterium lipopolysaccharide cyclooxygenase 2 immunoglobulin enhancer binding protein messenger RNA mitogen activated protein kinase p38 phosphatidylinositol 3 kinase protein kinase B reactive oxygen metabolite adrenal cortex cell animal cell article controlled study enzyme activity enzyme induction enzyme inhibition enzyme phosphorylation mouse nonhuman priority journal protein expression rat signal transduction Adrenocortical cells AKT/PKB Cyclooxygenase-2 Lipopolysaccharide p38 MAPK Adrenal Cortex Animals Antioxidants Cell Line, Tumor Chromones Cyclooxygenase 2 Enzyme Inhibitors Gene Expression Regulation Lipopolysaccharides Male Mice Morpholines p38 Mitogen-Activated Protein Kinases Phosphatidylinositol 3-Kinases Phosphorylation Primary Cell Culture Proto-Oncogene Proteins c-akt Rats Reactive Oxygen Species Signal Transduction Mercau, M.E. Astort, F. Giordanino, E.F. Martinez Calejman, C. Sanchez, R. Caldareri, L. Repetto, E.M. Coso, O.A. Cymeryng, C.B. Involvement of PI3K/Akt and p38 MAPK in the induction of COX-2 expression by bacterial lipopolysaccharide in murine adrenocortical cells
topic_facet	Adrenocortical cells AKT/PKB Cyclooxygenase-2 Lipopolysaccharide P38 MAPK 2 morpholino 8 phenylchromone bacterium lipopolysaccharide cyclooxygenase 2 immunoglobulin enhancer binding protein messenger RNA mitogen activated protein kinase p38 phosphatidylinositol 3 kinase protein kinase B reactive oxygen metabolite adrenal cortex cell animal cell article controlled study enzyme activity enzyme induction enzyme inhibition enzyme phosphorylation mouse nonhuman priority journal protein expression rat signal transduction Adrenocortical cells AKT/PKB Cyclooxygenase-2 Lipopolysaccharide p38 MAPK Adrenal Cortex Animals Antioxidants Cell Line, Tumor Chromones Cyclooxygenase 2 Enzyme Inhibitors Gene Expression Regulation Lipopolysaccharides Male Mice Morpholines p38 Mitogen-Activated Protein Kinases Phosphatidylinositol 3-Kinases Phosphorylation Primary Cell Culture Proto-Oncogene Proteins c-akt Rats Reactive Oxygen Species Signal Transduction
description	Previous studies from our laboratory demonstrated the involvement of COX-2 in the stimulation of steroid production by LPS in murine adrenocortical Y1 cells, as well as in the adrenal cortex of male Wistar rats. In this paper we analyzed signaling pathways involved in the induction of this key regulatory enzyme in adrenocortical cells and demonstrated that LPS triggers an increase in COX-2 mRNA levels by mechanisms involving the stimulation of reactive oxygen species (ROS) generation and the activation of p38 MAPK and Akt, in addition to the previously demonstrated increase in NFκB activity. In this sense we showed that: (1) inhibition of p38 MAPK or PI3K/Akt (pharmacological or molecular) prevented the increase in COX-2 protein levels by LPS, (2) LPS induced p38 MAPK and Akt phosphorylation, (3) antioxidant treatment blocked the effect of LPS on p38 MAPK phosphorylation and in COX-2 protein levels, (4) PI3K inhibition with LY294002 prevented p38 MAPK phosphorylation and, (5) the activity of an NFκB reporter was decreased by p38 MAPK or PI3K inhibition.These results suggest that activation of both p38 MAPK and PI3K/Akt pathways promote the stimulation of NFκB activity and that PI3K/Akt activity might regulate both p38 MAPK and NFκB signaling pathways.In summary, in this study we showed that in adrenal cells, LPS induces COX-2 expression by activating p38 MAPK and PI3K/Akt signaling pathways and that both pathways converge in the modulation of NFκB transcriptional activity. © 2014 Elsevier Ireland Ltd.
format	JOUR
author	Mercau, M.E. Astort, F. Giordanino, E.F. Martinez Calejman, C. Sanchez, R. Caldareri, L. Repetto, E.M. Coso, O.A. Cymeryng, C.B.
author_facet	Mercau, M.E. Astort, F. Giordanino, E.F. Martinez Calejman, C. Sanchez, R. Caldareri, L. Repetto, E.M. Coso, O.A. Cymeryng, C.B.
author_sort	Mercau, M.E.
title	Involvement of PI3K/Akt and p38 MAPK in the induction of COX-2 expression by bacterial lipopolysaccharide in murine adrenocortical cells
title_short	Involvement of PI3K/Akt and p38 MAPK in the induction of COX-2 expression by bacterial lipopolysaccharide in murine adrenocortical cells
title_full	Involvement of PI3K/Akt and p38 MAPK in the induction of COX-2 expression by bacterial lipopolysaccharide in murine adrenocortical cells
title_fullStr	Involvement of PI3K/Akt and p38 MAPK in the induction of COX-2 expression by bacterial lipopolysaccharide in murine adrenocortical cells
title_full_unstemmed	Involvement of PI3K/Akt and p38 MAPK in the induction of COX-2 expression by bacterial lipopolysaccharide in murine adrenocortical cells
title_sort	involvement of pi3k/akt and p38 mapk in the induction of cox-2 expression by bacterial lipopolysaccharide in murine adrenocortical cells
url	http://hdl.handle.net/20.500.12110/paper_03037207_v384_n1-2_p43_Mercau
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_version_	1807316073876291584

Involvement of PI3K/Akt and p38 MAPK in the induction of COX-2 expression by bacterial lipopolysaccharide in murine adrenocortical cells

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