The adverse effects of copper on the catecholaminergic nervous system have
been well documented and primarily attributed to its redox related properties. To
determine the significance of the redox properties of copper, a comprehensive study of
the catecholaminergic toxicity of Cu(II) has been carried out using MN9D, PC12 and
SH-SY5Y cells and compared the results with that of non-redox active Zn(II) and nonneuronal
HepG2 cells. While Cu(II) is more toxic than Zn(II), membrane permeable
metal chelators increase the toxicities of the both metals to catecholaminergic cells in
comparison to HepG2 cells. The toxicities of the two metals are parallel to their uptakes
and no protection from toxicity is observed with high concentrations of bathocuproine
which stabilizes the redox active Cu(I). Thus, the redox properties of Cu(II) are not the
primary cause of catecholaminergic toxicity. The increase of reactive oxygen species
(ROS) and the apoptotic DNA fragmentation induced by both metals suggest that the
apoptotic cell death is due to the excessive ROS production. Significance these findings
with respect to intracellular calcium perturbation is discussed.
Part II of my research is focused on structural characterization of cyt b561. The
protein was isolated from bovine adrenal glands and pre-steady state kinetics of
oxidized protein was carried out using stopped-flow absorption spectrophotometry. The
reduction kinetics was complex and would be fitted into a linear combination of three
exponential functions, providing further evidence for the presence of two heme b
centers in the protein. / Thesis (Ph.D.)--Wichita State University, College of Liberal Arts and Sciences, Dept. of Chemistry
| Identifer | oai:union.ndltd.org:WICHITA/oai:soar.wichita.edu:10057/5058 |
| Date | 07 1900 |
| Creators | Kollalpitiya, Konara Yamuna |
| Contributors | Wimalasena, Kandatege |
| Publisher | Wichita State University |
| Source Sets | Wichita State University |
| Language | en_US |
| Detected Language | English |
| Type | Dissertation |
| Format | xviii, 139 p. |
| Rights | © Copyright 2011 by Konara Y. Kollalpitiya. All rights reserved |
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