Two pathways of apoptosis are simultaneously induced in the embryonal brains of neural cell-specific HIF-1alpha-deficient mice.
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.
Ueno
Masaki
M
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
Tomita
Shuhei
S
Ueki
Masaaki
M
Iwanaga
Yasuyuki
Y
Huang
Cheng-Long
CL
Onodera
Masayuki
M
Maekawa
Nobuhiro
N
Gonzalez
Frank J
FJ
Sakamoto
Haruhiko
H
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
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