Masters Theses

Author

Hsiu-Jen Wang

Keywords and Phrases

Store-operated calcium entry

Abstract

"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.

Advisor(s)

Aronstam, Robert

Committee Member(s)

Ercal, Nuran
Huang, Yue-wern

Department(s)

Biological Sciences

Degree Name

M.S. in Applied and Environmental Biology

Publisher

Missouri University of Science and Technology

Publication Date

Fall 2010

Pagination

vii, 37 pages

Note about bibliography

Includes bibliographical references (pages 35-37).

Rights

© 2010 Hsiu-Jen Wang, All rights reserved.

Document Type

Thesis - Open Access

File Type

text

Language

English

Library of Congress Subject Headings

Calcium-binding proteins
Muscarinic receptors
Nanoparticles
Zinc oxide

Thesis Number

T 9763

Print OCLC #

723191226

Electronic OCLC #

694106039

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