Mitochondrial DNA damage and a hypoxic response are induced by CoCl2 in rat neuronal PC12 cells

Guichun Wang, Tapas Hazra, Sankar Mitra, Heung Man Lee, Ella Englander

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130 Citations (Scopus)

Abstract

Generation of reactive oxygen species (ROS) and activation of a transcriptional program that mimics the hypoxic response have been documented in cultured cells in the presence of cobalt chloride. We found that in the presence of hypoxia-mimicking concentrations of CoCl2, mitochondrial but not nuclear DNA damage is induced in rat neuronal, PC12 cells. To our knowledge, this is the first documentation of induction of mitochondrial DNA (mtDNA) damage under these conditions. Likewise, we provide the first evidence for elevation of MYH, the mammalian homolog of the Escherichia coli MutY DNA glycosylase, in mammalian cells. Recently, the human MYH was implicated in repair of oxidative DNA damage and shown to carry a mitochondrial localization sequence. Here, an induction of mtDNA damage and a time-dependent increase in the MYH level were detected with exposure of cells to 100 μM CoCl2. In addition, the levels of proteins involved in cellular responses to hypoxia, ROS and nuclear DNA damage; hypoxia-inducible factor 1α (HIF-1α), p53, p21 and PCNA were also modulated temporally. Earlier studies suggested that the mtDNA is a primary target for oxidative damage. Our findings extend these observations and suggest that activation of DNA repair processes is associated with the presence of mtDNA damage.

Original languageEnglish (US)
Pages (from-to)2135-2140
Number of pages6
JournalNucleic Acids Research
Volume28
Issue number10
StatePublished - May 15 2000

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PC12 Cells
Mitochondrial DNA
DNA Damage
Reactive Oxygen Species
DNA Glycosylases
Hypoxia-Inducible Factor 1
Proliferating Cell Nuclear Antigen
DNA Repair
Documentation
Transcriptional Activation
Cultured Cells
Escherichia coli
Proteins

ASJC Scopus subject areas

  • Genetics

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Mitochondrial DNA damage and a hypoxic response are induced by CoCl2 in rat neuronal PC12 cells. / Wang, Guichun; Hazra, Tapas; Mitra, Sankar; Lee, Heung Man; Englander, Ella.

In: Nucleic Acids Research, Vol. 28, No. 10, 15.05.2000, p. 2135-2140.

Research output: Contribution to journalArticle

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