A newly established neuronal ρ-0 cell line highly susceptible to oxidative stress accumulates iron and other metals: Relevance to the origin of metal ion deposits in brains with neurodegenerative disorders

Ryuichi Fukuyama, Akihiko Nakayama, Taizen Nakase, Hiroe Toba, Teruo Mukainaka, Hirofumi Sakaguchi, Takuya Saiwaki, Hiromu Sakurai, Mikio Wada, Shinji Fushiki

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

From human neuroblastoma-derived SILA cells we have established a ρ-0 cell line that is deficient in both respiration and mitochondrial DNA. Lactate dehydrogenase activity, lactate production, and growth in the medium without glucose indicate that these cells shift from aerobic to anaerobic metabolism. Electron microscopic observations revealed abnormal mitochondria with unique cristae structures. Staining with Mito-Tracker dye showed that the mitochondrial transmembrane potential was reduced by 30-40% from the parent cell levels. These cells were markedly susceptible to H2O2 and died apparently by a necrotic mechanism, a process blocked by deferoxamine in the parent cells but not ρ-0 cells. Analysis by inductively coupled plasmamass spectrometry revealed an approximately 3-fold accumulation of iron in the ρ-0 cells at confluence (n = 4-6, three clones, *p < 0.05). Iron and four other metals were all elevated in the cells of one of the ρ-0 clones and were similar to control levels in the control cybrid cells, which were replenished with normal mitochondrial DNA. Their sensitivity to H2O2 was also similar to that of the parent cells. These results indicate that a newly established neuronal related ρ-0 cell line is highly susceptible to active oxygen species and that these toxicity effects appear to be related to an accumulation of transition metals, which probably occurs through the respiratory impairment.

Original languageEnglish
Pages (from-to)41455-41462
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number44
DOIs
Publication statusPublished - 2002 Nov 1
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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