Apoptosis of leukemic lymphocytes mediated by purinergic P2z receptors
Peng, L.; Bradley, C.J.; Wiley, J.S.
Zhonghua Yi Xue Za Zhi 78(7): 508-511
1998
ISSN/ISBN: 0376-2491 PMID: 10923459 Document Number: 495689
To investigate the role of purinergic P2z receptors for apoptosis of human leukemic lymphocytes induced by extracellular adenosine triphosphate (ATP). A total of 11 B-CLL patients were studied with regard to exposure of leukemic lymphocytes with (n = 8) or without (n = 3) P2z receptors to ATP, benzoylbenzoic-ATP (BzATP), 2-methylthio-ATP (2MeSATP), adenosine-5'-[gamma-thio] triphosphate (ATP-gamma S), and other nucleosides for 8 h in vitro. Apoptosis was detected by electron microscopy (EM), agarose gel electrophoresis, and quantitative assay-TdT assay. Apoptosis was detected only in leukemic lymphocytes with P2z receptors. Using a quantitative assay, we found that ATP-induced DNA strand breaks occur specifically with BzATP, ATP and 2MeSATP, but not for analogue ATP-gamma S nor other nucleosides. Meanwhile, ATP-induced DNA fragmentation was fully blocked by pretreatment with oxidized ATP (OxATP), a compound recently shown to block P2z receptors. Also, the Ca2+/calmodulin complex played a role in the regulation of the apoptosis induced by ATP on CLL cells, because an antagonist of this complex, 1-[N,O-bis (5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62) was found to inhibit the ATP-induced apoptosis. These data indicate that P2z receptors on lymphocytes play an important role in apoptosis induced by ATP in vitro.