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Statins and ATP regulate nuclear pAkt via the P2X7 purinergic receptor in epithelial cells

Abstract

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.
Authors:
Mistafa, Oras; Hoegberg, Johan; [1]  Stenius, Ulla [1] 
  1. Institute of Environmental Medicine, Karolinska Institutet, Box 210, 17177 Stockholm (Sweden)
Publication Date:
Jan 04, 2008
Product Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 365; Journal Issue: 1; Other Information: DOI: 10.1016/j.bbrc.2007.10.148; PII: S0006-291X(07)02321-2; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Subject:
60 APPLIED LIFE SCIENCES; ATP; CHOLESTEROL; DRUGS; IN VIVO; INSULIN; METABOLISM; RECEPTORS
OSTI ID:
21033042
Country of Origin:
United States
Language:
English
Other Identifying Numbers:
Journal ID: ISSN 0006-291X; BBRCA9; TRN: US08R0230053249
Availability:
Available from http://dx.doi.org/10.1016/j.bbrc.2007.10.148;INIS
Submitting Site:
INIS
Size:
page(s) 131-136
Announcement Date:
Jun 20, 2008

Citation Formats

Mistafa, Oras, Hoegberg, Johan, and Stenius, Ulla. Statins and ATP regulate nuclear pAkt via the P2X7 purinergic receptor in epithelial cells. United States: N. p., 2008. Web. doi:10.1016/j.bbrc.2007.10.148.
Mistafa, Oras, Hoegberg, Johan, & Stenius, Ulla. Statins and ATP regulate nuclear pAkt via the P2X7 purinergic receptor in epithelial cells. United States. doi:10.1016/j.bbrc.2007.10.148.
Mistafa, Oras, Hoegberg, Johan, and Stenius, Ulla. 2008. "Statins and ATP regulate nuclear pAkt via the P2X7 purinergic receptor in epithelial cells." United States. doi:10.1016/j.bbrc.2007.10.148. https://www.osti.gov/servlets/purl/10.1016/j.bbrc.2007.10.148.
@misc{etde_21033042,
title = {Statins and ATP regulate nuclear pAkt via the P2X7 purinergic receptor in epithelial cells}
author = {Mistafa, Oras, Hoegberg, Johan, and Stenius, Ulla}
abstractNote = {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.}
doi = {10.1016/j.bbrc.2007.10.148}
journal = {Biochemical and Biophysical Research Communications}
issue = {1}
volume = {365}
place = {United States}
year = {2008}
month = {Jan}
}