RRC ID 11840
Author Shiraishi H, Okamoto H, Hara H, Yoshida H.
Title Alternative cell death of Apaf1-deficient neural progenitor cells induced by withdrawal of EGF or insulin.
Journal 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.
Volume 1800(3)
Pages 405-15
Published 2010-3
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 3.79
Times Cited 7
Mice GFP-LC3#53