NDLI: Mitochondrial DNA damage in iron overload.

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Mitochondrial DNA damage in iron overload.

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Mitochondrial DNA damage in iron overload.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Sun, Xiao-feng Campian, Jian Li Qian, Mingwei Gao, Xueshan Eaton, John W.
Description	Author Affiliation: Gao X ( Department of Oncology, University of Linköping, Linköping 58185, Sweden.)
Abstract	Chronic iron overload has slow and insidious effects on heart, liver, and other organs. Because iron-driven oxidation of most biologic materials (such as lipids and proteins) is readily repaired, this slow progression of organ damage implies some kind of biological 'memory.' We hypothesized that cumulative iron-catalyzed oxidant damage to mtDNA might occur in iron overload, perhaps explaining the often lethal cardiac dysfunction. Real time PCR was used to examine the 'intactness' of mttDNA in cultured H9c2 rat cardiac myocytes. After 3-5 days exposure to high iron, these cells exhibited damage to mtDNA reflected by diminished amounts of near full-length 15.9-kb PCR product with no change in the amounts of a 16.1-kb product from a nuclear gene. With the loss of intact mtDNA, cellular respiration declined and mRNAs for three electron transport chain subunits and 16 S rRNA encoded by mtDNA decreased, whereas no decrements were found in four subunits encoded by nuclear DNA. To examine the importance of the interactions of iron with metabolically generated reactive oxygen species, we compared the toxic effects of iron in wild-type and rho(o) cells. In wild-type cells, elevated iron caused increased production of reactive oxygen species, cytostasis, and cell death, whereas the rho(o) cells were unaffected. We conclude that long-term damage to cells and organs in iron-overload disorders involves interactions between iron and mitochondrial reactive oxygen species resulting in cumulative damage to mtDNA, impaired synthesis of respiratory chain subunits, and respiratory dysfunction.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	8
Volume Number	284
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2009-02-20
Publisher Place	United States
Access Restriction	Open
Subject Keyword	DNA Damage DNA, Mitochondrial Metabolism Iron Overload Myocytes, Cardiac Reactive Oxygen Species Animals Cell Line Drug Effects Electron Transport Pharmacology Pathology Oxidation-Reduction Oxygen Consumption Polymerase Chain Reaction RNA, Ribosomal, 16S Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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