Down-regulation of apurinic/apyrimidinic endonuclease expression is associated with the induction of apoptosis in differentiating myeloid leukemia cells

Kent A. Robertson, David P. Hill, Yi Xu, Lifei Liu, Steffany Van Epps, David M. Hockenbery, Jeff R. Park, Teresa M. Wilson, Mark R. Kelley

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Abstract

The human DNA repair enzyme apurinic/apyrimidinic endonuclease (APE/ref- 1) is a multifunctional protein in the DNA base excision repair (BER) pathway that is responsible for repair of apurinic/apyrimidinic (AP) sites in DNA. DNA repair and programmed cell death both function using different mechanisms to protect the organism from the consequences of extensive cellular damage; however, little is known about the relationship of the DNA BER repair pathway to apoptosis. We have determined the relationship of a BER DNA repair enzyme, APE, to apoptosis using the myeloid leukemia cell line HL-60, which can be induced to differentiate down the granulocytic or monocytic/macrophage pathway. Treatment of HL-60 cells with retinoic acid/DMSO (granulocytic) or phorbol 12-myristate 13-acetate (monocytic) results in apoptosis and in down- regulation of APE expression at both the RNA and protein levels. Moreover, double-labeling experiments using APE immunohistochemistry and the terminal deoxyribonucleotidyl transferase-mediated dUTP-fluorescein nick end labeling assay for apoptosis demonstrate that individual cells undergoing apoptosis lose expression of APE regardless of their state of differentiation. Blocking apoptosis by overexpression of the bcl-2 proto-oncogene in HL-60 cells or by a bcr-abl-related mechanism in K562 cells and subsequent differentiation results in morphological differentiation but no loss of APE expression. These studies establish that down-regulation of APE expression is associated with programmed cell death in cells of the myeloid lineage.

Original languageEnglish (US)
Pages (from-to)443-449
Number of pages7
JournalCell Growth and Differentiation
Volume8
Issue number4
StatePublished - Apr 1 1997

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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