Dopamine D1 receptor-mediated inhibition of NADPH oxidase activity in human kidney cells occurs via protein kinase A–protein kinase C cross talk
| Autor: | Francis B. Arnaldo, Robin A. Felder, Van Anthony M. Villar, Gisela P. Concepcion, Peiying Yu, Mark T. Quinn, Hewang Li, Weixing Han, Pedro A. Jose |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Fenoldopam
Dopamine Gene Expression Kidney Biochemistry Article chemistry.chemical_compound Enzyme activator Physiology (medical) medicine Humans Protein Isoforms Staurosporine Phosphorylation RNA Small Interfering Protein kinase A Protein Kinase Inhibitors Protein Kinase C Protein kinase C Cell Line Transformed Oxidase test NADPH oxidase biology Receptors Dopamine D1 NADPH Oxidases Cyclic AMP-Dependent Protein Kinases Molecular biology Enzyme Activation chemistry Phorbol biology.protein Tetradecanoylphorbol Acetate Signal Transduction medicine.drug |
| Zdroj: | Free Radical Biology and Medicine. 50:832-840 |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/j.freeradbiomed.2010.12.027 |
| Popis: | Dopamine cellular signaling, via the D1 receptor (D1R), involves both protein kinase A (PKA) and protein kinase C (PKC), but the PKC isoform involved has not been determined. Therefore, we tested the hypothesis that the D1R-mediated inhibition of NADPH oxidase activity involves cross-talk between PKA and specific PKC isoform(s). In HEK-293 cells heterologously expressing human D1R (HEK-hD1), fenoldopam, a D1R agonist, and phorbol-12-myristate-13-acetate (PMA), a PKC activator, inhibited oxidase activity in a time- and concentration-dependent manner. The D1R-mediated inhibition of oxidase activity (68.1±3.6%) was attenuated by two different PKA inhibitors, H89 (10 µmol/L) (88±8.1%) and Rp-cAMP (10 µmol/L) (97.7±6.7%), and two different PKC inhibitors, bisindolylmaleimide I (1 µmol/L) (94±6%) and staurosporine (10 nmol/L) (93±8%), which by themselves, had no effect (n=4–8/group). The inhibitory effect of PMA (1 µmol/L) on oxidase activity (73±3.2%) was blocked by H89 (100±7.8%) (n=5–6/group). The PMA-mediated inhibition of NADPH oxidase activity was accompanied by an increase in PKCθS676, an effect that was also blocked by H89. Fenoldopam (1 µmol/L) also increased PKCθS676 in HEK-hD1 and human renal proximal tubule (RPT) cells. Knockdown of PKCθ with siRNA in RPT cells prevented the inhibitory effect of fenoldopam on NADPH oxidase activity. Our studies demonstrate for the first time that cross-talk between PKA and PKCθ plays an important role in the D1R-mediated negative regulation of NADPH oxidase activity in human kidney cells. |
| Databáze: | OpenAIRE |
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