1. Progesterone synthesis by human placental mitochondria is sensitive to PKA inhibition by H89.
- Author
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Gomez-Concha C, Flores-Herrera O, Olvera-Sanchez S, Espinosa-Garcia MT, and Martinez F
- Subjects
- A Kinase Anchor Proteins metabolism, Enzyme Assays, Female, Humans, Mitochondria enzymology, Mitochondria metabolism, Oxygen Consumption, Phosphoproteins metabolism, Phosphorylation, Placenta cytology, Placenta metabolism, Pregnancy, Protein Stability, Protein Tyrosine Phosphatases, Non-Receptor metabolism, Trophoblasts enzymology, Trophoblasts metabolism, Cyclic AMP-Dependent Protein Kinases antagonists & inhibitors, Isoquinolines pharmacology, Mitochondria drug effects, Placenta drug effects, Progesterone biosynthesis, Sulfonamides pharmacology, Trophoblasts drug effects
- 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., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2011
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