論文 - 詳細
RRC ID | 11840 |
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著者 | Shiraishi H, Okamoto H, Hara H, Yoshida H. |
タイトル | Alternative cell death of Apaf1-deficient neural progenitor cells induced by withdrawal of EGF or insulin. |
ジャーナル | Biochim Biophys Acta |
Abstract |
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. |
巻・号 | 1800(3) |
ページ | 405-15 |
公開日 | 2010-3-1 |
DOI | 10.1016/j.bbagen.2009.11.008 |
PII | S0304-4165(09)00315-8 |
PMID | 19914347 |
MeSH | Animals Antioxidants / pharmacology Apoptosis / drug effects Apoptotic Protease-Activating Factor 1 / deficiency* Apoptotic Protease-Activating Factor 1 / genetics Cell Death / drug effects Cell Death / physiology* Cell Division / drug effects Crosses, Genetic DNA Primers Epidermal Growth Factor / pharmacology* Genotype Insulin / pharmacology* Kinetics Mice Mice, Knockout Neurons / cytology Neurons / drug effects Neurons / physiology* Stem Cells / cytology Stem Cells / drug effects Stem Cells / physiology* Thapsigargin / pharmacology Tunicamycin / pharmacology |
IF | 3.411 |
引用数 | 7 |
WOS 分野 | BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY |
リソース情報 | |
実験動物マウス | RBRC00806 |