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 - 2001/8/29
Y1 - 2001/8/29
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
C2 - 11570579
AN - SCOPUS:0034880557
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 -