Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 1998
[Study on apoptosis of leukemic lymphocytes mediated by purinergic P2z receptors].
Аннотация на английскомСтатьяНазвание и аннотация: Перевод пока не подготовлен
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Peng L, Bradley C J, Wiley J S
Аннотация
OBJECTIVE: To investigate the role of purinergic P2z receptors in human leukemic lymphocyte apoptosis induced by extracellular adenosine triphosphate (ATP).
METHODS: Eleven B-CLL patients were studied. Leukemic lymphocytes with (n = 8) or without (n = 3) P2z receptors were exposed in vitro to ATP, benzoyl-benzoic-ATP (BzATP), 2-methylthio-ATP(2MeSATP), adenosine-5'-[gamma-thio] triphosphate (ATP-gamma S), and other nucleosides for 8 h. Apoptosis was detected by electron microscopy (EM), agarose gel electrophoresis, and quantitative TdT assay.
RESULTS: Apoptosis was detected only in leukemic lymphocytes with P2z receptors. By using the quantitative assay, ATP-inducing DNA strand breaks were found to occur specifically for BzATP, ATP and 2MeSATP, but not for ATP-gamma S and other nucleosides. Meanwhile, ATP-inducing DNA fragmentation was fully blocked by pretreatment with oxidized ATP (OxATP), a compound recently shown to block P2z receptors. Ca2+/Calmodulin complex played a role in the regulation of the CLL cell apoptosis induced by ATP, 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-inducing apoptosis.
CONCLUSION: P2z receptors on lymphocytes play an important role in the apoptosis induced by ATP in vitro.
METHODS: Eleven B-CLL patients were studied. Leukemic lymphocytes with (n = 8) or without (n = 3) P2z receptors were exposed in vitro to ATP, benzoyl-benzoic-ATP (BzATP), 2-methylthio-ATP(2MeSATP), adenosine-5'-[gamma-thio] triphosphate (ATP-gamma S), and other nucleosides for 8 h. Apoptosis was detected by electron microscopy (EM), agarose gel electrophoresis, and quantitative TdT assay.
RESULTS: Apoptosis was detected only in leukemic lymphocytes with P2z receptors. By using the quantitative assay, ATP-inducing DNA strand breaks were found to occur specifically for BzATP, ATP and 2MeSATP, but not for ATP-gamma S and other nucleosides. Meanwhile, ATP-inducing DNA fragmentation was fully blocked by pretreatment with oxidized ATP (OxATP), a compound recently shown to block P2z receptors. Ca2+/Calmodulin complex played a role in the regulation of the CLL cell apoptosis induced by ATP, 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-inducing apoptosis.
CONCLUSION: P2z receptors on lymphocytes play an important role in the apoptosis induced by ATP in vitro.