α7 nicotinic acetylcholine receptors control cytochrome c release from isolated mitochondria through kinase-mediated pathways
| Autor: | Serhiy Komisarenko, Olena Lykhmus, Galyna Gergalova, Maryna Skok |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
alpha7 Nicotinic Acetylcholine Receptor Aconitine Mitochondria Liver Nicotinic Antagonists Biology Biochemistry Wortmannin Bridged Bicyclo Compounds Mice Phosphatidylinositol 3-Kinases chemistry.chemical_compound Ganglion type nicotinic receptor Superoxides medicine Animals Nicotinic Agonists Phosphorylation Protein Kinase Inhibitors Protein Kinase C Phosphoinositide-3 Kinase Inhibitors Acetylcholine receptor Cytochromes c Cell Biology Androstadienes Mice Inbred C57BL Nicotinic acetylcholine receptor src-Family Kinases Nicotinic agonist chemistry Benzamides Signal transduction Alpha-4 beta-2 nicotinic receptor Calcium-Calmodulin-Dependent Protein Kinase Type 2 Protein Kinases Proto-Oncogene Proteins c-akt Acetylcholine Signal Transduction medicine.drug |
| Zdroj: | The International Journal of Biochemistry & Cell Biology. 49:26-31 |
| ISSN: | 1357-2725 |
| Popis: | Nicotinic acetylcholine receptors are ligand-gated ion channels found in the plasma membrane of both excitable and non-excitable cells. Previously we reported that nicotinic receptors containing α7 subunits were present in the outer membranes of mitochondria to regulate the early apoptotic events like cytochrome c release. Here we show that signaling of mitochondrial α7 nicotinic receptors affects intramitochondrial protein kinases. Agonist of α7 nicotinic receptors PNU 282987 (30 nM) prevented the effect of phosphatidyl inositol-3-kinase inhibitor wortmannin, which stimulated cytochrome c release in isolated mouse liver mitochondria, and restored the Akt (Ser 473) phosphorylation state decreased by either 90 μM Ca2+ or wortmannin. The effect of PNU 282987 was similar to inhibition of calcium-calmodulin-dependent kinase II (upon 90 μM Ca2+) or of Src kinase(s) (upon 0.5 mM H2O2) and of protein kinase C. Cytochrome c release from mitochondria could be also attenuated by α7 nicotinic receptor antagonist methyllicaconitine or α7-specific antibodies. Allosteric modulator PNU 120526 (1 μM) did not improve the effect of agonist PNU 282987. Acetylcholine (1 μM) and methyllicaconitine (10 nM) inhibited superoxide release from mitochondria measured according to alkalization of Ca2+-containing medium. It is concluded that α7 nicotinic receptors regulate mitochondrial permeability transition pore formation through ion-independent mechanism involving activation of intramitochondrial PI3K/Akt pathway and inhibition of calcium-calmodulin-dependent or Src-kinase-dependent signaling pathways. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect