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Myeloperoxidase: a myeloid cell nuclear antigen with DNA-binding properties

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
An antigen histochemically localized in the nuclei and cytoplasmic granules of normal and leukemic human myeloid cells has been identified as myeloperoxidase. The localization and amount of the enzyme was determined by using a murine monoclonal antibody designated H-43-5 raised against nuclear proteins derived from human promyelocytic HL-60 leukemia cells. The highest amount of nuclear MPO was found in granulocytes; less than half of this amount was detected in nuclei from HL-60 cells. MPO from HL-60 cells was purified by immunoaffinity chromatography, fractionated into three components (forms I, II, and III) by CM-cellulose chromatography, and measured using radioimmunoassay. Chromatography of these MPO forms on DNA-Sepharose columns confirmed that all three forms of MPO were tightly bound to DNA with apparent relative affinities in the order of form III > form II > form I. The affinity of MPO form III for DNA was sufficient to enable the formation and elution of DNA-MPO complexes during size-exclusion chromatography at high ionic strength and neutral pH. This form of MPO was also able to shield DNA from strand scission induced by active oxygen species generated by xanthine oxidase acting aerobically on xanthine. These data suggest that intranuclear MPO may help to protect DNA against damage resulting from oxygen radicals produced during myeloid cell maturation and function.
Research Organization:
Argonne National Lab., IL (USA)
DOE Contract Number:
W-31109-ENG-38
OSTI ID:
6652072
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Journal Issue: 4 Vol. 85:4; ISSN PNASA
Country of Publication:
United States
Language:
English