Macrophage migration inhibitory factor induces phosphorylation of Mdm2 mediated by phosphatidylinositol 3-kinase/Akt kinase: Role of this pathway in decidual cell survival |
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| Affiliation: | 1. Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil;2. Department of Stomatology, Dental School, University of São Paulo, São Paulo, Brazil;3. Department of Life Sciences, University of Siena, Siena, Italy;1. Department of Cell Biology, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City, Mexico;2. Department of Endocrinology, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City, Mexico;3. Department of Rheumatology, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City, Mexico;4. Department of Nutrition, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City, Mexico;5. Unidad de Vinculación Faculty of Medicine, UNAM en el INMEGEN, Mexico City, Mexico;1. Department of Life Sciences, National Central University, Jhongli, Taoyuan 320, Taiwan;2. Taoyuan Armed Forces General Hospital, Longtan, Taoyuan 325, Taiwan;1. Programa de Pós-Graduação em Biologia Celular e Molecular, Universidade Federal do Rio Grande do Sul, Caixa Postal 15005, CEP 91501-970 Porto Alegre, RS, Brazil;2. Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, CEP 91501-970 Porto Alegre, RS, Brazil;3. Graduação em Biotecnologia, Universidade Federal do Rio Grande do Sul, Caixa Postal 15005, CEP 91501-970 Porto Alegre, RS, Brazil;1. Department of Oncology and Radiotherapy, Charles University in Prague, Medical Faculty and University Hospital in Hradec Králové, Czech Republic;2. Department of Gynecology, Charles University in Prague, Medical Faculty and University Hospital in Hradec Králové, Czech Republic;3. 4th Department of Internal Medicine – Haematology, Charles University in Prague, Medical Faculty and University Hospital in Hradec Králové, Czech Republic;1. Department of Experimental Oncology, Academic Drug Discovery Program, and Drug Development Program, European Institute of Oncology, Via Adamello, Milan 20139, Italy;2. Department of Biosciences, University of Milan, Via Celoria 26, Milan 20100, Italy |
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| Abstract: | The phosphatidylinositol 3-kinase (PI3K)/Akt pathway has an anti-apoptotic effect through several downstream targets, which includes activation of the transformed mouse 3T3 cell double-minute 2 (Mdm2) protein, its translocation to the nucleus and degradation of the tumor suppressor p53. We show that Mif, the Macrophage Migration Inhibitory Factor, an important cytokine at the maternal fetal interface in several species, triggers phosphorylation of Mdm2 protein in a PI3K/Akt-dependent manner, thereby preventing apoptosis in cultured mouse decidual cells. Inhibition of Akt and PI3K suppresses the pathway. Mif treatment also changes the nuclear translocation of p53 and interferes with the apoptotic fate of these cells when challenged with reactive oxygen species. In conclusion, an important mechanism has been found underlying decidual cell survival through Akt signaling pathway activated by Mif, suggesting a role for this cytokine in decidual homeostasis and in the integrity of the maternal-fetal barrier that is essential for successful gestation. |
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| Keywords: | MIF" },{" #name" :" keyword" ," $" :{" id" :" kwrd0015" }," $$" :[{" #name" :" text" ," _" :" Human macrophage migration inhibitory factor Mif" },{" #name" :" keyword" ," $" :{" id" :" kwrd0025" }," $$" :[{" #name" :" text" ," _" :" mouse macrophage migration inhibitory factor mrMif" },{" #name" :" keyword" ," $" :{" id" :" kwrd0035" }," $$" :[{" #name" :" text" ," _" :" mouse recombinant macrophage migration inhibitory factor PI3K" },{" #name" :" keyword" ," $" :{" id" :" kwrd0045" }," $$" :[{" #name" :" text" ," _" :" phosphatidylinositol 3-Kinase Mdm2" },{" #name" :" keyword" ," $" :{" id" :" kwrd0055" }," $$" :[{" #name" :" text" ," _" :" transformed mouse 3T3 cell double-minute 2 Akt" },{" #name" :" keyword" ," $" :{" id" :" kwrd0065" }," $$" :[{" #name" :" text" ," _" :" protein kinase B LY or LY294002" },{" #name" :" keyword" ," $" :{" id" :" kwrd0075" }," $$" :[{" #name" :" text" ," _" :" 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) WT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0085" }," $$" :[{" #name" :" text" ," _" :" Wortmannin TRIC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0095" }," $$" :[{" #name" :" text" ," _" :" triciribine DAPI" },{" #name" :" keyword" ," $" :{" id" :" kwrd0105" }," $$" :[{" #name" :" text" ," _" :" 4, 6-diamidino-2-phenylindole |
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