Keywords and Phrases
Store-operated calcium entry
"The influences of ZnO nanoparticles on cellular responses to activation of muscarinic receptors were studied in Chinese hamster ovary cells expressing the human M3 muscarinic acetylcholine receptor. ZnO particles (20 nm) induced cytotoxicity in a time and concentration-dependent manner: following a 24 h exposure, toxicity was minimal at concentrations below 20 µg/ml but virtually complete at concentrations above 28 µg/ml. ZnO particles did not affect antagonist binding to M3 receptors or allosteric ligand effects, but increased agonist binding affinity while eliminating guanine nucleotide sensitivity. At a noncytotoxic concentration (10 µg/ml), ZnO increased resting [Ca²⁺]i from 40 to 130 nM without compromising calcium homeostatic mechanisms. ZnO particles had minimal effects on inositol 1,4,5-trisphosphate (IP3)- or thapsigargin-mediated release of intracellular calcium from the endoplasmic reticulum, but strongly inhibited store operated calcium entry (capacitive calcium entry). The latter effect was seen as 1) a decrease in the plateau phase of the response and 2) a decrease in Ca²⁺ entry upon introduction of calcium to the extracellular medium following thapsigargin-induced depletion of calcium from the endoplasmic reticulum (EC50's [approximately] 2 µg/ml). Thus, ZnO nanoparticles interfere with two specific aspects of the M3 signaling pathway, agonist binding and store operated calcium entry"--Abstract, page iii.
M.S. in Applied and Environmental Biology
Missouri University of Science and Technology
vii, 37 pages
© 2010 Hsiu-Jen Wang, All rights reserved.
Thesis - Open Access
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Link to Catalog Record
Wang, Hsiu-Jen, "Zinc oxide nanoparticle disruption of store-operated calcium entry in a muscarinic receptor signaling pathway" (2010). Masters Theses. 6922.