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.
Hung
Amos C
AC
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
Porter
Alan G
AG
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