Cyclosporin A inhibits 2-chloroadenosine-induced DNA cleavage in mouse thymocytes.
Incubation of mouse thymocytes with the adenosine analogue 2-chloroadenosine resulted in enhanced internucleosomal DNA fragmentation which could be inhibited by the immunosuppressive drug cyclosporin A. In order to be effective, cyclosporin A had to be added to thymocyte preparations at the same time as 2-chloroadenosine. Since cyclosporin A is a selective inhibitor of calcineurin, our data suggest a possible role for calcineurin as a signaling intermediate in the apoptotic pathway activated in thymocytes through adenosine receptors. However, at the present time we cannot exclude the possibility that the inhibitory effect of cyclosporin A on 2-chloroadenosine-induced apoptosis may be mediated through a calcineurin-independent process.
Makrigiannis
A P
AP
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
Blay
J
J
Hoskin
D W
DW
D015762:2-Chloroadenosine / Q000037:antagonists & inhibitors*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000502:physiology; D016572:Cyclosporine / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010749:Phosphoprotein Phosphatases / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology
D002148:Calmodulin-Binding Proteins; D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D015762:2-Chloroadenosine; D016572:Cyclosporine; D004247:DNA; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases