Extracellular ATP modulates podocyte function through P2Y purinergic receptors and pleiotropic effects on AMPK and cAMP/PKA signaling pathways
| Autor: | Irena Audzeyenka, Stefan Angielski, Dorota Rogacka, Maria Szrejder, Agnieszka Piwkowska, Michał Rychłowski, Patrycja Rachubik |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
rho GTP-Binding Proteins P2Y receptor RHOA Biophysics AMP-Activated Protein Kinases Biochemistry Second Messenger Systems Podocyte 03 medical and health sciences Adenosine Triphosphate medicine Cyclic AMP Animals Rats Wistar Molecular Biology 030102 biochemistry & molecular biology biology Chemistry Podocytes Receptors Purinergic P2 Purinergic receptor Purinergic signalling Actin cytoskeleton Cyclic AMP-Dependent Protein Kinases Cell biology Rats 030104 developmental biology medicine.anatomical_structure biology.protein Glomerular Filtration Barrier Female Signal transduction |
| Zdroj: | Archives of biochemistry and biophysics. 695 |
| ISSN: | 1096-0384 |
| Popis: | Podocytes and their foot processes interlinked by slit diaphragms, constitute a continuous outermost layer of the glomerular capillary and seem to be crucial for maintaining the integrity of the glomerular filtration barrier. Purinergic signaling is involved in a wide range of physiological processes in the renal system, including regulating glomerular filtration. We evaluated the role of nucleotide receptors in cultured rat podocytes using non-selective P2 receptor agonists and agonists specific for the P2Y1, P2Y2, and P2Y4 receptors. The results showed that extracellular ATP evokes cAMP-dependent pathways through P2 receptors and influences remodeling of the podocyte cytoskeleton and podocyte permeability to albumin via coupling with RhoA signaling. Our findings highlight the relevance of the P2Y4 receptor in protein kinase A-mediated signal transduction to the actin cytoskeleton. We observed increased cAMP concentration and decreased RhoA activity after treatment with a P2Y4 agonist. Moreover, protein kinase A inhibitors reversed P2Y4-induced changes in RhoA activity and intracellular F-actin staining. P2Y4 stimulation resulted in enhanced AMPK phosphorylation and reduced reactive oxygen species generation. Our findings identify P2Y-PKA-RhoA signaling as the regulatory mechanism of the podocyte contractile apparatus and glomerular filtration. We describe a protection mechanism for the glomerular barrier linked to reduced oxidative stress and reestablished energy balance. |
| Databáze: | OpenAIRE |
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