Consequences of iron regulatory protein regulation during hypoxia

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Title Consequences of iron regulatory protein regulation during hypoxia
Publication Type dissertation
School or College School of Medicine
Department Oncological Sciences
Author Schneider, Brian Douglas
Date 2004-05
Description Iron is an essential element that is required for survival of all living organisms. Although all organism require iron, excess iron can be toxic through its ability to catalyze the production of reactive oxygen species (ROS) via Fenton chemistry. Thus, the control of intracellular free ion levels plays a significant role in ROS production. Iron homeostasis in maintained by the iron regulatory proteins (IRP1 and IRP2). The IRPs control intracellular free iron levels by regulating the synthesis of the transferrin receptor (TfR), a protein involved in iron uptake, and ferritin (Ft), an iron storage protein. Given the relationship between iron and oxygen in the production of ROS and the regulation of iron homeostasis by the IRP system, it has been shown that the IRPs are differentially regulated by hypoxia, a physiologically relevant condition of low oxygen involved in human diseases. This thesis describes the research to determine the cellular consequences if IRP regulation and elucidate the role of each IRP in the maintenance of iron homeostasis during hypoxia in mammalian cells. The data show that hypoxia causes the differential regulation of IRPs, which is reversible upon reoxygenation (ReO2), in both tumorigenic and primary cell culture models. Ft expression is also regulated during both hypoxia and ReO2 with no change in TfR protein. Hypoxia causes a transient increase in Ft synthesis, which may be independent of the IRP system in primary cells. Interestingly, Ft protein accumulates during hypoxia in primary cells, while decreasing in tumorigenic cells. These data suggest that Ft expression may influence susceptibility to cell damage during hypoxia and ReO2. This work further our understanding of how cells regulate Ft synthesis and maintain iron homeostasis during a pathophysiological condition that has implications for the treatment of human diseases where iron is involved.
Type Text
Publisher University of Utah
Subject Metabolism; Physiology
Subject MESH Iron; Anoxemia
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "© Consequences of iron regulatory protein regulation during hypoxia". Spencer S. Eccles Health Sciences Library. Print version of "Consequences of iron regulatory protein regulation during hypoxia". available at J. Willard Marriott Library Special Collection. QP6.5 2004 .S35.
Rights Management © Brian Douglas Schneider.
Format application/pdf
Format Medium application/pdf
Format Extent 2,063,675 bytes
Identifier undthes,4584
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
Master File Extent 2,063,690 bytes
ARK ark:/87278/s61n82vf
Setname ir_etd
ID 190505
Reference URL https://collections.lib.utah.edu/ark:/87278/s61n82vf
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