TY - JOUR
T1 - Hypoxia enhances β-amyloid-induced apoptosis in rat cultured hippocampal neurons
AU - Egashira, Nobuaki
AU - Iwasaki, Katsunori
AU - Ishibashi, Motoki
AU - Hatip-Al-Khatib, Izzetin
AU - Wolozin, Benjamin
AU - Mishima, Kenichi
AU - Irie, Keiichi
AU - Fujiwara, Michihiro
PY - 2002/12/1
Y1 - 2002/12/1
N2 - We investigated the effect of hypoxia on β-amyloid (Aβ)-induced apoptosis in rat cultured hippocampal neurons. Aβ (25 μM 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 Aβ and hypoxia (Aβ/hypoxia) significantly enhanced in decrease in the number of neuronal cells and the increase in the number of TUNEL-positive cells. Z-Asp-CH2-DCB, an inhibitor of interleukin-1β-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 Aβ/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.
AB - We investigated the effect of hypoxia on β-amyloid (Aβ)-induced apoptosis in rat cultured hippocampal neurons. Aβ (25 μM 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 Aβ and hypoxia (Aβ/hypoxia) significantly enhanced in decrease in the number of neuronal cells and the increase in the number of TUNEL-positive cells. Z-Asp-CH2-DCB, an inhibitor of interleukin-1β-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 Aβ/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.
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U2 - 10.1254/jjp.90.321
DO - 10.1254/jjp.90.321
M3 - Article
C2 - 12501008
AN - SCOPUS:0036956436
VL - 90
SP - 321
EP - 327
JO - Japanese Journal of Pharmacology
JF - Japanese Journal of Pharmacology
SN - 0021-5198
IS - 4
ER -