title: Two pathways of apoptosis are simultaneously induced in the embryonal brains of neural cell-specific HIF-1alpha-deficient mice.
abstract: The aim of this study was to clarify the mechanism of apoptosis seen in the cortex of neural cell-specific hypoxia inducible factor-1alpha (HIF-1alpha)-deficient embryos. A previous study showed that the neural cells in the cortical area of the mutant embryos underwent apoptosis coincident with vascular regression. Through histological, immunohistochemical, and electron microscopic technique, two kinds of apoptotic cells were detected in the mutant embryonal cortex. Apoptotic cells of one type were clustered in small round structures, 10-20 mum in diameter, whereas the others, present in large numbers, were distributed in a group at the cortical plate located more to the outer side than the round structures. The histochemical and electron microscopic findings indicate that the former represented the appearance of macrophages, in which cellular fragments including vascular cells underwent oxidative stress-related, TNF receptor-mediated, caspase-2-induced apoptosis, while the latter showed c-Myc-related, caspase-3-activated apoptosis of the neural cells. These results suggest that two pathways of apoptosis are induced in neuronal and vascular cells of the cortex in the neural cell-specific HIF-1alpha-deficient mouse.
authors.affiliation: Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan. masaueno@med.kagawa-u.ac.jp
authors.forename: Masaki
authors.initials: M
authors.lastname: Ueno
authors.forename: Shuhei
authors.initials: S
authors.lastname: Tomita
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ueki
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Iwanaga
authors.forename: Cheng-Long
authors.initials: CL
authors.lastname: Huang
authors.forename: Masayuki
authors.initials: M
authors.lastname: Onodera
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Maekawa
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sakamoto
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000196:embryology*; D053143:Caspase 2 / Q000032:analysis; D053148:Caspase 3 / Q000032:analysis; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000172:deficiency*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D018613:Microscopy, Confocal; D009474:Neurons / Q000166:cytology; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016271:Proto-Oncogene Proteins c-myc; D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D014409:Tumor Necrosis Factor-alpha; C505409:Casp3 protein, mouse; D053143:Caspase 2; D053148:Caspase 3