title: Oxygen-induced mitochondrial biogenesis in the rat hippocampus.
abstract: The hypothesis that damage to mitochondrial DNA by reactive oxygen species increases the activity of nuclear and mitochondrial transcription factors for mitochondrial DNA replication was tested in the in vivo rat brain. Mitochondrial reactive oxygen species generation was stimulated using pre-convulsive doses of hyperbaric oxygen and hippocampal mitochondrial DNA content and neuronal and mitochondrial morphology and cell proliferation were evaluated at 1, 5 and 10 days. Gene expression was subsequently evaluated to assess nuclear and mitochondrial-encoded respiratory genes, mitochondrial transcription factor A, and nuclear respiratory transcription factors-1 and -2. After 1 day, a mitochondrial DNA deletion emerged involving Complex I and IV subunit-encoding regions that was independent of overt neurological or cytological O(2) toxicity, and resolved before the onset of cell proliferation. This damage was attenuated by blockade of neuronal nitric oxide synthase. Compensatory responses were found in nuclear gene expression for manganese superoxide dismutase, mitochondrial transcription factor A, and nuclear respiratory transcription factor-2. Enhanced nuclear respiratory transcription factor-2 binding activity in hippocampus was accompanied by a nearly three-fold boost in mitochondrial DNA content over 5 days. The finding that O(2) activates regional mitochondrial DNA transcription, replication, and mitochondrial biogenesis in the hippocampus may have important implications for maintaining neuronal viability after brain injury.
authors.affiliation: Department of Medicine and Anesthesiology and Center for Hyperbaric Medicine and Environmental Physiology, Duke University Medical Center, Box 3315, Durham, NC 27710, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Gutsaeva
authors.forename: H B
authors.initials: HB
authors.lastname: Suliman
authors.forename: M S
authors.initials: MS
authors.lastname: Carraway
authors.forename: I T
authors.initials: IT
authors.lastname: Demchenko
authors.forename: C A
authors.initials: CA
authors.lastname: Piantadosi
mesh_terms: D000818:Animals; D048430:Cell Shape / Q000187:drug effects / Q000502:physiology; D004261:DNA Replication / Q000187:drug effects / Q000502:physiology; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004579:Electron Transport / Q000187:drug effects / Q000235:genetics; D051268:GA-Binding Protein Transcription Factor / Q000187:drug effects / Q000378:metabolism; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000187:drug effects / Q000378:metabolism; D051266:Nuclear Respiratory Factor 1 / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism* / Q000494:pharmacology; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D004272:DNA, Mitochondrial; D051268:GA-Binding Protein Transcription Factor; D051266:Nuclear Respiratory Factor 1; D017382:Reactive Oxygen Species; C489030:Tfam protein, rat; D014157:Transcription Factors; D052248:Nitric Oxide Synthase Type I; D010100:Oxygen