Thymidine-dependent attenuation of the mitochondrial apoptotic pathway in adenosine-induced apoptosis of HL-60 cells

Chang Mo Kang, Yousin Suh, Ik Soon Jang, Sang Park

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Objective: We previously reported that adenosine-induced apoptosis in HL-60 cells was attenuated by cotreating the cells with pyrimidine nucleosides. The mechanism involved in this adenosine-induced apoptosis by the differential supply of nucleosides is studied here with a particular focus on the regulation of apoptosis-associated mitochondrial events. Methods: Time-dependent changes in the mitochondrial membrane potential (MMP) after treatment with adenosine and/or thymidine were monitored. Results: The cells did not show any decrease of MMP level up to 2.5 h after 1 mM adenosine exposure, whereas cytochrome c release, caspase-9 and caspase-3 activity, and DNA fragmentation were already activated, suggesting that mitochondrial depolarization is not a prerequisite of other apoptosis-related mitochondrial events. In contrast, the translocation of Bax to mitochondria and the release of cytochrome c began within the first hour of adenosine treatment. Conclusion: Thus, it is believed that adenosine-induced apoptosis is mediated by the activation of the caspase cascade by cytochrome c release with concomitant increase of Bax in the mitochondria, which implies that the translocation of Bax might be a leading event in the adenosine-induced apoptosis. Moreover, we found that most of the apoptotic parameters in adenosine-induced cellular changes, such as translocation of Bax, the release of cytochrome c, and the consequent activation of caspase-9 and caspase-3, were attenuated by thymidine supplement, thus indicating that the sensing of a nucleoside or nucleotide balance might be an upstream event of cytochrome c release. Therefore, it can be concluded that thymidine can attenuate adenosine-induced apoptosis by modulating the earliest stage of the mitochondrial apoptotic pathway.

Original languageEnglish (US)
Pages (from-to)570-576
Number of pages7
JournalJournal of Cancer Research and Clinical Oncology
Volume127
Issue number9
DOIs
StatePublished - Aug 29 2001

Keywords

  • Adenosine
  • Apoptosis
  • Bax translocation
  • Cytochrome c
  • Mitochondria
  • Thymidine

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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