β淀粉样肽_(1-40)通过激活caspase-3诱导大鼠皮层神经元凋亡

ACTIVATION OF caspase-3 DURING APOPTOSIS OF RAT CORTICAL NEURONS INDUCED BY β-AP_(1-40)

目的 探讨半胱氨酸蛋白酶caspase 3在 β淀粉样肽1 4 0 (β AP1 4 0 )诱导大鼠皮层神经元凋亡中的可能作用。 方法 用 β AP1 4 0 诱导神经元凋亡 ,同时检测caspase 3活力和caspase 3活性片段及caspase 3mRNA的表达水平。 结果 4 0mg·L- 1 的凝聚态 β AP1 4 0 诱导大鼠皮层神经元凋亡过程中 ,caspase 3活力和caspase 3mRNA的表达水平均有明显增高 (P <0 0 1) ;特异性的caspase 3抑制剂Ac DEVD CHO对caspase 3的激活和皮层神经元细胞凋亡均有明显的阻断作用。 结论 caspase 3可能是 β AP1 4 0

Objective To investigate the effects of caspase\|3 on β ΑΡ 1 40 induced apoptosis in rat cortical neurons. Methods Apoptosis was induced by 40?mg\5L -1 β\|AP 1 40 .The apoptotic neurons were observed by TUNEL staining and DNA gel electrophoresis.The activity and mRNA expression of caspase\|3 was measured by fluorescent spectrofluorometer and RT\|PCR.The cleaved caspase\|3 was detected with immunocytochemistry. Results After treatment with β\|AP 1\|40 ,the rat cortical neurons showed DNA fragmentation.The expression of caspase\|3 mRNA ratio to β actin was 0\^78,0\^85 and 0\^39 respectively after treatment for 12,24 and 48?h.Caspase\|3 activity was 133 24±7 47,192 16±11 03,88 87±4 24 MFI\5μg protein -1 \5h -1 .The cleaved caspase\|3 was observed within cytoplasm.Specific inhibitor of caspase\|3 Ac\|DEVD\|CHO inhibited caspase\|3 activation and blocked cortical neurons apoptosis markedly.Conclusion\ Caspase\|3 might be an executor during β AP 1 40 induced apoptosis in rat cortical neurons.[