کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4328811 | 1614190 | 2009 | 7 صفحه PDF | دانلود رایگان |
Previously, this laboratory found that apoptosis was augmented significantly in fetal rhombencephalic neurons when they were treated with 50 mM ethanol for 24 h. These changes were associated temporally with a reduction in the phosphatidylinositol 3-kinase (PI3K) pro-survival pathway and in the downstream expression of several NF-κB dependent anti-apoptotic genes. The serotonin-1A agonist ipsapirone prevented ethanol-associated apoptosis; it also activated the PI3K → pAkt pro-survival pathway and the expression of specific NF-κB dependent anti-apoptotic genes in ethanol-treated neurons. The present study investigated the temporal effects of both ethanol and ipsapirone on the expression of three NF-κB dependent genes, XIAP, Bcl-xl and catalase; these genes encode proteins that could potentially attenuate ethanol-induced apoptosis. Catalase activity was also measured. All three genes demonstrated an early activation by ethanol. After a brief treatment with 50 mM ethanol, i.e., 2 to 8 h depending on the gene, the expression of XIAP, Bcl-xl, and catalase was significantly increased, possibly as an initial attempt to survive. An ethanol-associated increase in catalase was followed by a rise in catalase activity. However, when ethanol treatment was continued for a longer time, there was a significant reduction in both XIAP and Bcl-xl. In addition, both catalase expression and activity returned to levels found in unstressed controls. Importantly, treatment with ipsapirone augmented the activity of catalase and the expression of Bcl-xl, XIAP, and catalase in ethanol-treated neurons at later time points. The latter effects are likely to contribute to the pro-survival effects of ipsapirone.
Journal: Brain Research - Volume 1249, 16 January 2009, Pages 54–60