title: Progesterone synthesis by human placental mitochondria is sensitive to PKA inhibition by H89.
abstract: The transfer of cholesterol to mitochondria, which might involve the phosphorylation of proteins, is the rate-limiting step in human placental steroidogenesis. Protein kinase A (PKA) activity and its role in progesterone synthesis by human placental mitochondria were assessed in this study. The results showed that PKA and phosphotyrosine phosphatase D1 are associated with syncytiotrophoblast mitochondrial membrane by an anchoring kinase cAMP protein-121. The ³²P-labeled of four major proteins was analyzed. The specific inhibitor of PKA, H89, decreased progesterone synthesis in mitochondria while in mitochondrial steroidogenic contact sites protein-phosphorylation was diminished, suggesting that PKA plays a role in placental hormone synthesis. In isolated mitochondria, PKA activity was unaffected by the addition of cAMP suggesting a constant activity of this kinase in the syncytiotrophoblast. The presence of PKA and phosphotyrosine phosphatase D1 anchored to mitochondria by an anchoring kinase cAMP protein-121 indicated that syncytiotrophoblast mitochondria contain a full phosphorylation/dephosphorylation system.
authors.affiliation: Departamento de Bioquimica, Facultad de Medicina, Universidad Nacional Autónoma de México, Apartado Postal 70-159, Coyoacan 04510, Mexico, D.F., Mexico.
authors.forename: Cuauhtemoc
authors.initials: C
authors.lastname: Gomez-Concha
authors.forename: Oscar
authors.initials: O
authors.lastname: Flores-Herrera
authors.forename: Sofia
authors.initials: S
authors.lastname: Olvera-Sanchez
authors.forename: Ma Teresa
authors.initials: MT
authors.lastname: Espinosa-Garcia
authors.forename: Federico
authors.initials: F
authors.lastname: Martinez
mesh_terms: D054758:A Kinase Anchor Proteins / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D057075:Enzyme Assays; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010101:Oxygen Consumption; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D010920:Placenta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000096:biosynthesis*; D055550:Protein Stability; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D014327:Trophoblasts / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
chemical_list: D054758:A Kinase Anchor Proteins; C105137:AKAP1 protein, human; D007546:Isoquinolines; D010750:Phosphoproteins; D013449:Sulfonamides; D011374:Progesterone; D017868:Cyclic AMP-Dependent Protein Kinases; C409985:PTPN21 protein, human; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide