Disruption of Muscarinic Receptor Mediated Signal Transduction by Oxidative Stress
Department
Biological Sciences
Major
Biological Sciences
Research Advisor
Aronstam, Robert
Advisor's Department
Biological Sciences
Funding Source
Missouri S&T cDNA Resource Center
Abstract
The ability of a series of metal oxide nanoparticles (20 - 60 nm) to alter muscarinic receptor signaling was studied in cells with the human M3 muscarinic acetylcholine receptor. Activation of M3 receptors induced a biphasic increase in [Ca2+]i: an initial, IP3-mediated release of Ca2+ from endoplasmic reticulum (ER) stores followed by a sustained phase of Ca2+ entry (i.e., store operated calcium entry, SOCE). The different particles had multiple effects on calcium metabolism and muscarinic signaling: resting calcium concentration was increased and SOCE entry was decreased among other effects. Only ZnO and CuO particles consistently increased resting [Ca2+]i. SOCE was depressed by several metal oxide particles in disparate degrees. ZnO depressed most aspects of calcium signaling in response to muscarinic stimulation. The effect of SOCE depression did not correlate highly with cytotoxicity. The present findings raise the possibility that nanoparticle-induced cytotoxicity and nanoparticle-induced SOCE depression have different mechanisms of action.
Biography
Joshua is a current senior at the Missouri University of Science and Technology. He has worked under the tutelage of Dr. Robert Aronstam on the subject of muscarinic receptors and how different toxins affect their signaling properties since August 2009. He is planning on attending medical school in the upcoming academic year and has already been accepted to the Saint Louis School of Medicine.
Research Category
Sciences
Presentation Type
Poster Presentation
Document Type
Poster
Location
Upper Atrium/Hallway
Presentation Date
06 Apr 2011, 9:00 am - 11:45 am
Disruption of Muscarinic Receptor Mediated Signal Transduction by Oxidative Stress
Upper Atrium/Hallway
The ability of a series of metal oxide nanoparticles (20 - 60 nm) to alter muscarinic receptor signaling was studied in cells with the human M3 muscarinic acetylcholine receptor. Activation of M3 receptors induced a biphasic increase in [Ca2+]i: an initial, IP3-mediated release of Ca2+ from endoplasmic reticulum (ER) stores followed by a sustained phase of Ca2+ entry (i.e., store operated calcium entry, SOCE). The different particles had multiple effects on calcium metabolism and muscarinic signaling: resting calcium concentration was increased and SOCE entry was decreased among other effects. Only ZnO and CuO particles consistently increased resting [Ca2+]i. SOCE was depressed by several metal oxide particles in disparate degrees. ZnO depressed most aspects of calcium signaling in response to muscarinic stimulation. The effect of SOCE depression did not correlate highly with cytotoxicity. The present findings raise the possibility that nanoparticle-induced cytotoxicity and nanoparticle-induced SOCE depression have different mechanisms of action.
