Homocysteine thiolactone induces apoptotic DNA damage mediated by increased intracellular hydrogen peroxide and caspase 3 activation in HL-60 cells

Rwei Fen S. Huang*, Sheu Mai Huang, Bou Shu Lin, Jeng Shu Wei, Tsan Zon Liu

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

125 Scopus citations

Abstract

The cytotoxicity of homocysteine derivatives on chromosomal damage in somatic cells is not well established. The present study used reactive homocysteine derivative of homocysteine thiolactone (Hcy) to investigate its causal effect on apoptotic DNA injury in human promyeloid HL-60 cells. Our results demonstrated that Hcy induced cell death and features of apoptosis including increased phosphotidylserine exposure on the membrane surface, increased apoptotic cells with hypoploid DNA contents, and internucleosomal DNA fragmentation, all of which occurred in a time- and concentration-dependent manner. Hcy treatment also significantly increased intracellular reactive oxygen species H2O2, which coincided with the elimination of caspase 3 proenzyme levels and increased caspase 3 activity at the time of the appearance of apoptotic DNA fragmentation. Preincubation of Hcy-treated HL-60 cells with catalase completely scavenged intracellular H2O2, thus inhibiting caspase 3 activity and protecting cells from apoptotic DNA damage. In contrast, superoxide dismutase failed to inhibit Hcy-induced DNA damage. Taken together, these results demonstrate that Hcy exerted its genotoxic effects on HL-60 cells through an apoptotic pathway, which is mediated by the activation of caspase 3 activity induced by an increase in intracellular hydrogen peroxide.

Original languageEnglish
Pages (from-to)2799-2811
Number of pages13
JournalLife Sciences
Volume68
Issue number25
DOIs
StatePublished - 11 05 2001

Keywords

  • Apoptosis
  • Caspase 3
  • Homocysteine thiolactone
  • Hydrogen peroxide

Fingerprint

Dive into the research topics of 'Homocysteine thiolactone induces apoptotic DNA damage mediated by increased intracellular hydrogen peroxide and caspase 3 activation in HL-60 cells'. Together they form a unique fingerprint.

Cite this