Hypoxia enhances beta-amyloid-induced apoptosis in rat cultured hippocampal neurons.
We investigated the effect of hypoxia on beta-amyloid (Abeta)-induced apoptosis in rat cultured hippocampal neurons. Abeta (25 microM for 48 h) decreased the number of neuronal cells and increased the number of TUNEL-positive cells. Hypoxia (6 h) also decreased the number of neuronal cells, but did not increase the number of TUNEL-positive cells. Moreover, combined treatment with both Abeta and hypoxia (Abeta/hypoxia) significantly enhanced the decrease in the number of neuronal cells and the increase in the number of TUNEL-positive cells. Z-Asp-CH(2)-DCB, an inhibitor of interleukin-1beta-converting enzyme (ICE), or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-N-methyl-D-aspartate (non-NMDA) receptor antagonist, decreased the number of TUNEL-positive cells with Abeta/hypoxia. These findings suggest that ischemia or hypoxia is an important factor that facilitates the symptoms of Alzheimer's disease and that non-NMDA receptors are involved in the induction of apoptosis in patients suffering from both cerebrovascular disease and Alzheimer's disease.
Egashira
Nobuaki
N
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan.
Iwasaki
Katsunori
K
Ishibashi
Motoki
M
Hatip-Al-Khatib
Izzetin
I
Wolozin
Benjamin
B
Mishima
Kenichi
K
Irie
Keiichi
K
Fujiwara
Michihiro
M
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004622:Embryo, Mammalian; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D008954:Models, Biological; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione