Splenic B lymphocyte programmed cell death is prevented by nitric oxide release through mechanisms involving sustained Bcl-2 levels.
Incubation of ex vivo cultured mature B cells in the presence of nitric oxide or nitric oxide-donor substances delays programmed cell death as determined by the appearance of DNA laddering in agarose gel electrophoresis or by flow-cytometry analysis of DNA. Nitric oxide also rescues B cells from antigen-induced apoptosis but fails to provide a co-stimulatory signal that converts the signal elicited by the antigen into a proliferative response. The protective effects of nitric oxide against programmed cell death can be reproduced by treatment of the cells with permeant analogues of cyclic GMP. Regarding the mechanisms by which nitric oxide prevents apoptosis in B cells, we have observed that nitric oxide release prevents the drop in the expression of the protooncogene bcl-2, both at the mRNA and protein levels, suggesting the existence of an unknown pathway that links nitric oxide signaling with Bcl-2 expression.
Genaro
A M
AM
Instituto de Bioquímica (Centro Mixto CSIC-UCM), Facultad de Farmacia, Madrid, Spain.
Hortelano
S
S
Alvarez
A
A
Martínez
C
C
Boscá
L
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000473:pathology; D002470:Cell Survival; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism; D005434:Flow Cytometry; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D014158:Transcription, Genetic
D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D009569:Nitric Oxide; D019204:GTP-Binding Proteins; D006152:Cyclic GMP