| First Author | Shiraishi H | Year | 2010 |
| Journal | Biochim Biophys Acta | Volume | 1800 |
| Issue | 3 | Pages | 405-15 |
| PubMed ID | 19914347 | Mgi Jnum | J:164823 |
| Mgi Id | MGI:4835366 | Doi | 10.1016/j.bbagen.2009.11.008 |
| Citation | Shiraishi H, et al. (2010) Alternative cell death of Apaf1-deficient neural progenitor cells induced by withdrawal of EGF or insulin. Biochim Biophys Acta 1800(3):405-15 |
| abstractText | BACKGROUND: Various forms of cell death, such as apoptotic, autophagic and non-lysosomal types, are implicated in normal physiological processes. Apoptotic protease activating factor 1 (Apaf1) is an important component of the intrinsic apoptotic pathway. Deficiency of Apaf1 results in an accumulation of neural progenitor cells (NPCs) in the developing central nervous system and thus, in perinatal lethality. A small percentage of the mutant mice, however, are viable and grow to maturity. The occurrence of such normal mutants implicates alternative cell death pathways during neurogenesis. METHODS: NPCs prepared from wild-type or Apaf1-deficient embryos were cultured in growth factor-deprived medium and examined for cell death, caspase activation and morphological alterations. Generation of reactive oxygen species (ROS) and the effects of antioxidants were examined. RESULTS: Wild-type NPCs underwent apoptosis within 24 hours of withdrawal of epidermal growth factor (EGF) or insulin, whereas Apaf1-deficient NPCs underwent cell death but showed no signs of apoptosis. Autophagy was not necessarily accompanied by cell death. Cell death of the Apaf1-deficient NPCs resembled necroptosis-necrosis-like programmed cell death. The necroptosis inhibitor necrostatin-1, however, failed to inhibit the cell death. ROS accumulation was detected in NPCs deprived of growth factors, and an antioxidant partially suppressed the non-apoptotic cell death of Apaf1-deficient NPCs. CONCLUSIONS: These data indicate that after withdrawal EGF or insulin withdrawal, the Apaf1-deficient cells underwent non-apoptotic cell death. ROS generation may partially participate in the cell death. GENERAL SIGNIFICANCE: Non-apoptotic cell death in NPCs may be a compensatory mechanism in the developing CNS of Apaf1-deficient embryos. |
