Elucidation of cGMP-dependent induction of mitochondrial biogenesis through PKG and p38 MAPK in the kidney
| Autor: | Pallavi Bhargava, Jaroslav Janda, Rick G. Schnellmann |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Physiology p38 mitogen-activated protein kinases Carbazoles Enzyme Activators Dibenzocycloheptenes 030204 cardiovascular system & hematology Mitochondrion Kidney p38 Mitogen-Activated Protein Kinases 03 medical and health sciences 0302 clinical medicine Formoterol Fumarate Cyclic GMP-Dependent Protein Kinases medicine Animals Phosphorylation Receptor Cyclic GMP Protein Kinase Inhibitors Cells Cultured Organelle Biogenesis Rapid Report biology Chemistry Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Mitochondria Cell biology Enzyme Activation Fluorobenzenes Pyrimidines 030104 developmental biology Mitochondrial biogenesis Mitogen-activated protein kinase cardiovascular system biology.protein Pyrazoles Female Rabbits Formoterol cGMP-dependent protein kinase Biogenesis Signal Transduction medicine.drug |
| Zdroj: | Am J Physiol Renal Physiol |
| ISSN: | 1522-1466 1931-857X |
| Popis: | Previous studies have shown that cGMP increases mitochondrial biogenesis (MB). Our laboratory has determined that formoterol and LY344864, agonists of the β2-adrenergic receptor and 5-HT1F receptor, respectively, signal MB in a soluble guanylyl cyclase (sGC)-dependent manner. However, the pathway between cGMP and MB produced by these pharmacological agents in renal proximal tubule cells (RPTCs) and the kidney has not been determined. In the present study, we showed that treatment of RPTCs with formoterol, LY344864, or riociguat, a sGC stimulator, induces MB through protein kinase G (PKG), a target of cGMP, and p38, an associated downstream target of PKG and a regulator of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) expression in RPTCs. We also examined if p38 plays a role in PGC-1α phosphorylation in vivo. Administration of l-skepinone, a potent and specific inhibitor of p38α and p38β, to naïve mice inhibited phosphorylated PGC-1α localization in the nuclear fraction of the renal cortex. Taken together, we demonstrated a pathway, sGC/cGMP/PKG/p38/PGC-1α, for pharmacological induction of MB and the importance of p38 in this pathway. |
| Databáze: | OpenAIRE |
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