Rat MYH, a glycosylase for repair of oxidatively damaged DNA, has brain-specific isoforms that localize to neuronal mitochondria

Ella W. Englander, Zhaoyong Hu, Abha Sharma, Heung Man Lee, Zhao Hui Wu, George H Greeley

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Mitochondrial genomes are exposed to a heavy load of reactive oxygen species (ROS) that damage DNA. Since in neurons, mitochondrial DNA integrity must be maintained over the entire mammalian life span, neuronal mitochondria most likely repair oxidatively damaged DNA. We show that the Escherichia coli MutY DNA glycosylase homolog (MYH) in rat (rMYH) involved in repair of oxidative damage is abundantly expressed in the rat brain, with isoforms that are exclusive to brain tissue. Confocal microscopy and western analyses reveal localization of rMYH in neuronal mitochondria. To assess involvement of MYH in the neuronal response to oxidative DNA damage, we used a rat model of respiratory hypoxia, in which acutely reduced blood oxygenation leads to generation of superoxide, and formation and subsequent removal of 8-hydroxy-2′-deoxyguanosine (8OHdG). Removal of 8OHdG is accompanied by a spatial increase in rMYH immunoreactivity in the brain and an increase in levels of one of the three mitochondrial MYH isoforms, suggesting that inducible and non-inducible MYH isoforms exist in the brain. The mitochondrial localization of oxidative DNA damage repair enzymes in neurons may represent a specialized neuronal mechanism that safeguards mitochondrial genomes in the face of routine and accidental exposures to heavy loads of injurious ROS.

Original languageEnglish (US)
Pages (from-to)1471-1480
Number of pages10
JournalJournal of neurochemistry
Volume83
Issue number6
DOIs
StatePublished - Dec 2002

Keywords

  • 7,8-dihydro-8-oxoguanine
  • DNA repair
  • Hypoxia
  • MYH
  • Mitochondria
  • Rat brain

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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