c-fos,bax和p53的反义寡聚核苷酸(ASOs)对溶血磷脂酸所致的培养小鼠大脑皮层神经元凋亡的影响(英文)

Effects of antisense oligodeoxynucleotides against c-fos,bax,and p53 mRNAs upon apoptosis induced by lysophosphatidic acid in cultured cortical neurons

溶血磷脂酸(lysophosphatidic acid,LPA)在高浓度时( >50μmol/L)显示出对培养大脑皮层神经元致凋亡特性。本研究旨在初步分析溶血磷脂酸致凋亡过程中对相关基因表达的依赖性,在研究中结合琼脂糖电泳,HO33342染色和TUNEL技术观察c-fos,bax和p53三种反义寡聚核苷酸对溶血磷脂酸致培养大脑皮层神经元致凋亡的影响。结果显示结合c-fos, bax和p53三种反义寡聚核苷酸均表现出对溶血磷脂酸致凋亡的神经保护作用。溶血磷脂酸的致凋亡过程为c-fos,bax和p53基因依赖性,不同于b淀粉样蛋白片段31 -35的致凋亡特性。

It has been reported that lysophosphatidic acid（LPA） at excessive concentrations （ 〉 50 μmol/L）act as an apoptogenic factor in cultured cortical neurons. The present study was designed to evaluate if the LPA-induced apoptosis relied on similar alterations in genomic expression as that in apoptosis induced by other apoptogenic agents or neuronal insults. Antisense oligodeoxynucleotides（ASO） against c-fos, bax, and p53 mRNA were tested, respectively. Eletrophoresis, HO33342 staining, and TUNEL examinations were used to examine the existence of apoptotic neurons. The results showed that ASOs against c-fos, bax and p53 exhibited neuroprotective effects upon the apoptosis induced by lysophosphatidie acid in cultured cortical neurons. This suggests that the expression of these three genes are indispensable for the LPA-induced apoptosis, showing a different genomic basis as compared to that for AbP31 -35-induced apoptosis.