p53 mediates nitric oxide-induced apoptosis in murine neural progenitor cells.
Studies have shown that nitric oxide (NO)-induced apoptosis is mediated by a variety of cellular signaling pathways. However, the information is relatively limited to neural progenitor cells (NPCs). In this study, the role of p53 in the NO-induced apoptosis was examined in an in vitro model of NPCs. Comparisons were made between NPCs derived from either wild type or p53 knockout mice brain stimulated by diethylenetriamine/nitric oxide adduct (DETA/NO), an established NO donor that constantly releases NO through its known first order pharmacological kinetics and prolonged half-life. We found that treatment by DETA/NO both time- and dose-dependently induced a significant increase of apoptosis in wild type NPCs, while p53 knockout NPCs were resistant to the DETA/NO challenge. In addition, the DETA/NO-triggered alteration of mitochondrial membrane permeability, cleavage of caspase-9/3, and expression of pro-apoptotic Bcl-2 family members noxa and puma occurred in wild type NPCs but not in p53 knockout NPCs. Our current results suggest a central role of p53 in the NO-induced apoptotic pathway in NPCs, which may hence provide new insights into the regulation of cell death in NPCs that respond to overproduction of NO in injured brain.
Cell Death and Human Disease Group, Division of Cancer and Developmental Cell Biology, Institute of Molecular and Cell Biology, Singapore. amos.hung@utas.edu.au
Amos C
AC
Hung
Alan G
AG
Porter
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014226:Triazenes / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
C105351:1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene; D051017:Apoptosis Regulatory Proteins; D020030:Nitric Oxide Donors; C488588:PUMA protein, mouse; C408009:Pmaip1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D014226:Triazenes; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D009569:Nitric Oxide; D053453:Caspase 9