Title

Disruption of Muscarinic Receptor Mediated Signal Transduction by Oxidative Stress

Presenter Information

Joshua Erickson

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

This document is currently not available here.

Share

COinS
 
Apr 6th, 9:00 AM Apr 6th, 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.