Statins and ATP regulate nuclear pAkt via the P2X7 purinergic receptor in epithelial cells.
Many studies have documented P2X7 receptor functions in cells of mesenchymal origin. P2X7 is also expressed in epithelial cells and its role in these cells remains largely unknown. Our data indicate that P2X7 regulate nuclear pAkt in epithelial cells. We show that low concentration of atorvastatin, a drug inhibiting HMG-CoA reductase and cholesterol metabolism, or the natural agonist extracellular ATP rapidly decreased the level of insulin-induced phosphorylated Akt in the nucleus. This effect was seen within minutes and was inhibited by P2X7 inhibitors. Experiments employing P2X7 siRNA and HEK293 cells heterologously expressing P2X7 and in vivo experiments further supported an involvement of P2X7. These data indicate that extracellular ATP and statins via the P2X7 receptor modulate insulin-induced Akt signaling in epithelial cells.
Mistafa
Oras
O
Institute of Environmental Medicine, Karolinska Institutet, Box 210, 17177 Stockholm, Sweden.
Högberg
Johan
J
Stenius
Ulla
U
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D000069059:Atorvastatin; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000201:enzymology / Q000378:metabolism*; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7; D015398:Signal Transduction
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C546468:P2RX7 protein, human; D011758:Pyrroles; D034741:RNA, Small Interfering; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate; D000069059:Atorvastatin; D051057:Proto-Oncogene Proteins c-akt