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Gene expression profiling of copper ...

Armendariz, Angela Dawn.

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Gene expression profiling of copper overload states.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Gene expression profiling of copper overload states./
Author:	Armendariz, Angela Dawn.
Description:	145 p.
Notes:	Source: Dissertation Abstracts International, Volume: 66-02, Section: B, page: 0822.
Contained By:	Dissertation Abstracts International66-02B.
Subject:	Health Sciences, Nutrition. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3165287
ISBN:	0542007053

Gene expression profiling of copper overload states.
Armendariz, Angela Dawn.

Gene expression profiling of copper overload states. - 145 p.

Source: Dissertation Abstracts International, Volume: 66-02, Section: B, page: 0822.

Thesis (Ph.D.)--University of California, Berkeley, 2004.

Copper is a trace metal required by all organisms for survival. It is unknown whether transcription of the genes involved in copper transport is regulated by copper in mammalian systems. Additionally, the protective systems that operate in cells chronically exposed to copper, and the levels at which copper becomes toxic have not been identified. Finally, there is a need for an early biomarker of exposure to copper. The work in this dissertation was carried out to address these issues. We hypothesized that novel genes regulated by copper would be identified by cDNA microarray analysis of copper overload states in cells, and that specific patterns of gene expression characteristic of copper overload would be identified.

ISBN: 0542007053Subjects--Topical Terms:

1017801
Health Sciences, Nutrition.

Gene expression profiling of copper overload states.
LDR:03680nmm 2200313 4500 001 1816622
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020 $a 0542007053
035 $a (UnM)AAI3165287
035 $a AAI3165287
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100 1 $a Armendariz, Angela Dawn. $3 1905998
245 1 0 $a Gene expression profiling of copper overload states.
300 $a 145 p.
500 $a Source: Dissertation Abstracts International, Volume: 66-02, Section: B, page: 0822.
500 $a Chair: Christopher Vulpe.
502 $a Thesis (Ph.D.)--University of California, Berkeley, 2004.
520 $a Copper is a trace metal required by all organisms for survival. It is unknown whether transcription of the genes involved in copper transport is regulated by copper in mammalian systems. Additionally, the protective systems that operate in cells chronically exposed to copper, and the levels at which copper becomes toxic have not been identified. Finally, there is a need for an early biomarker of exposure to copper. The work in this dissertation was carried out to address these issues. We hypothesized that novel genes regulated by copper would be identified by cDNA microarray analysis of copper overload states in cells, and that specific patterns of gene expression characteristic of copper overload would be identified.
520 $a In the first study, "Gene Expression Profiling in Chronic Copper Overload Reveals Up-Regulation of App and Prnp," cells from genetic models of copper overload---fibroblast cells from two mouse mutants, C57BL/6-Atp7aMobr and C57BL/6- Atp7aModap were utilized. This work, using recently developed outlier identification methods to analyze microarrays, identified twelve genes that were differentially expressed in both cells lines. We suggest that these genes are candidate components potentially responsible for a copper specific homeostatic response. Two of the twelve genes encode copper-binding proteins not previously known to be copper-regulated at the transcription level-Amyloid beta precursor protein (App) and Prion protein (Prnp). This study adds weight to previous suggestions that both proteins might play a role in protection from copper overload.
520 $a The second study, "Gene Expression Profiling in Metallothionein KO mouse fibroblast cell lines," was an investigation of the effects of copper overload in cells lacking metallothionein to determine compensatory mechanisms that function to protect cells from excess copper. cDNA microarray analysis was used to examine the effects that loss of metal lothionein, a copper sequestering protein, had on gene expression. Microarray results suggest that the metal lothionein-deficient (MT-/-) cells, when under copper excess conditions, surprisingly, do not respond with induction of typical markers of cellular stress. Future research will help us to understand the observed effects in detail.
520 $a Overall, this work shows that insight into the complex mechanisms of uptake, delivery, detoxification and removal of copper can be gained by examining copper overload states using cDNA microarray analysis. This research identified novel genes regulated by copper overload; future studies will determine the specificity of this regulation. Finally, this work suggests that changes in patterns of gene expression may allow differentiation of chronic versus acute exposure to copper.
590 $a School code: 0028.
650 4 $a Health Sciences, Nutrition. $3 1017801
650 4 $a Biology, Molecular. $3 1017719
690 $a 0570
690 $a 0307
710 2 0 $a University of California, Berkeley. $3 687832
773 0 $t Dissertation Abstracts International $g 66-02B.
790 1 0 $a Vulpe, Christopher, $e advisor
790 $a 0028
791 $a Ph.D.
792 $a 2004
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3165287