Hypoxia induces mitochondrial DNA damage and stimulates expression of a DNA repair enzyme, the Escherichia coli muty DNA glycosylase homolog (MYH), in vivo, in the rat brain

Heung Man Lee, Cheng Wang, Zhaoyong Hu, George H. Greeley, Wojciech Makalowski, Helen Hellmich, Ella Englander

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Hypoxia-associated, acutely reduced blood oxygenation can compromise energy metabolism, alter oxidant/antioxidant balance and damage cellular components, including DNA. We show in vivo, in the rat brain that respiratory hypoxia leads to formation of the oxidative DNA lesion, 8-hydroxy-2′-deoxyguanosine (oh8dG), a biomarker for oxidative DNA damage and to increased expression of a DNA repair enzyme involved in protection of the genome from the mutagenic consequences of oh8dG. The enzyme is a homolog of the Escherichia coli MutY DNA glycosylase (MYH), which excises adenine residues misincorporated opposite the oxidized base, oh8dG. We have cloned a full-length rat MYH (rMYH) cDNA, which encodes 516 amino acids, and by in situ hybridization analysis obtained expression patterns of rMYH mRNA in hippocampal, cortical and cerebellar regions. Ensuing hypoxia, mitochondrial DNA damage was induced and rMYH expression strongly elevated. This is the first evidence for a regulated expression of a DNA repair enzyme in the context of respiratory hypoxia. Our findings support the premise that oxidative DNA damage is repaired in neurons and the possibility that the hypoxia-induced expression of a DNA repair enzyme in the brain represents an adaptive mechanism for protection of neuronal DNA from injurious consequences of disrupted energy metabolism and oxidant/antioxidant homeostasis.

Original languageEnglish (US)
Pages (from-to)928-937
Number of pages10
JournalJournal of Neurochemistry
Volume80
Issue number5
DOIs
StatePublished - 2002

Fingerprint

DNA Glycosylases
DNA Repair Enzymes
Mitochondrial DNA
Escherichia coli
DNA Damage
Rats
Brain
DNA
Oxidants
Energy Metabolism
Antioxidants
Brain Hypoxia
Adenine
Oxygenation
In Situ Hybridization
Biomarkers
Homeostasis
Complementary DNA
Neurons
Genome

Keywords

  • Blood oxygenation
  • Cloning
  • DNA repair
  • Hypoxia
  • MutY DNA glycosylase
  • Rat brain

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Hypoxia induces mitochondrial DNA damage and stimulates expression of a DNA repair enzyme, the Escherichia coli muty DNA glycosylase homolog (MYH), in vivo, in the rat brain. / Lee, Heung Man; Wang, Cheng; Hu, Zhaoyong; Greeley, George H.; Makalowski, Wojciech; Hellmich, Helen; Englander, Ella.

In: Journal of Neurochemistry, Vol. 80, No. 5, 2002, p. 928-937.

Research output: Contribution to journalArticle

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