H-ferritin binds to DNA and protects DNA from iron-induced oxidative damage

K. Thompson, Z. Ye, M. Fried, James Connor

Research output: Contribution to journalArticle

Abstract

Ferritin (FRT). normally considered a cytosolic Fe storage protein, has been detected immunohistochemically in neuronal nuclei in mouse, rat, porcine, and human brains, hepato-cytes, enterocytes, epithelial colls and various CNS derived cell lines. Ferritin consists of 24 subunits of H and L chains but only the H is detected in nuclei. The experi-mental data reported here is based on studies with a human astrocytoma cell line (SW1088). Nuclear FRT is detected immediately after plating cells. Immunohistochemical detection of nuclear FRT i:An be eliminated after 24-36 hour treatment post plating with the Fe chelator desferral. The desferral effect is reversible by returning cells to standard media. FITC-FRT added to the media can be detected in the nucleus of cells in 30 minutes if the cells have been pretreated with desferral and permeablized. Recombinant H FRT possessed DNA binding activity that was detectable by EMSA. but recombinant L FRT and a mutant H FRT (222) lacking ferroxidase activity was not. Cross-linking studies on cells show that ferritin is associated with nuclear DNA. Ferritin binding to DNA in vitro doesn't appear sequence specific. Recombinant H FRT protected DNA from Fe-induced DNA single strand breaks. At similar protein concentrations the 222 mutant was 65% as effective and apoferrjtin 35% as effective. These results suggest that ferritin plays a, important role in protecting the DNA from Fe-catalyzed damage. The roll cycle stage at which FRT is present in the nucleus appears variable but cell .Specific. However, cells undergoing mitosis have no detectable FRT in the nudcns. Those observations indicate a novel and critical role for ferritin in DNA protection.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number8
StatePublished - Dec 1 1998

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All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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