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 Citations (Scopus)

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 - 2001
Externally publishedYes

Fingerprint

HL-60 Cells
Adenosine
Thymidine
Apoptosis
Cytochromes c
Caspase 9
Mitochondrial Membrane Potential
Nucleosides
Caspase 3
Mitochondria
Pyrimidine Nucleosides
DNA Fragmentation
Caspases
Nucleotides

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Thymidine-dependent attenuation of the mitochondrial apoptotic pathway in adenosine-induced apoptosis of HL-60 cells. / Kang, Chang Mo; Suh, Yousin; Jang, Ik Soon; Park, Sang.

In: Journal of Cancer Research and Clinical Oncology, Vol. 127, No. 9, 2001, p. 570-576.

Research output: Contribution to journalArticle

@article{0d78c1d1d8804ff1bc46e8c9f5886b73,
title = "Thymidine-dependent attenuation of the mitochondrial apoptotic pathway in adenosine-induced apoptosis of HL-60 cells",
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.",
keywords = "Adenosine, Apoptosis, Bax translocation, Cytochrome c, Mitochondria, Thymidine",
author = "Kang, {Chang Mo} and Yousin Suh and Jang, {Ik Soon} and Sang Park",
year = "2001",
doi = "10.1007/s004320100264",
language = "English (US)",
volume = "127",
pages = "570--576",
journal = "Journal of Cancer Research and Clinical Oncology",
issn = "0171-5216",
publisher = "Springer Verlag",
number = "9",

}

TY - JOUR

T1 - Thymidine-dependent attenuation of the mitochondrial apoptotic pathway in adenosine-induced apoptosis of HL-60 cells

AU - Kang, Chang Mo

AU - Suh, Yousin

AU - Jang, Ik Soon

AU - Park, Sang

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

KW - Adenosine

KW - Apoptosis

KW - Bax translocation

KW - Cytochrome c

KW - Mitochondria

KW - Thymidine

UR - http://www.scopus.com/inward/record.url?scp=0034880557&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034880557&partnerID=8YFLogxK

U2 - 10.1007/s004320100264

DO - 10.1007/s004320100264

M3 - Article

VL - 127

SP - 570

EP - 576

JO - Journal of Cancer Research and Clinical Oncology

JF - Journal of Cancer Research and Clinical Oncology

SN - 0171-5216

IS - 9

ER -