Chen M, Quintans J, Fuks Z, Thompson C, Kufe D W, Weichselbaum R R
Department of Radiation and Cellular Oncology, University of Chicago, Illinois 60637.
Cancer Res. 1995 Mar 1;55(5):991-4.
Recent studies have proposed that tumor necrosis factor alpha (TNF-alpha) and ionizing radiation induce apoptosis by activating hydrolysis of sphingomyelin to ceramide. Bcl-2 and a related gene, Bcl-X, inhibit several forms of apoptosis. Herein, we report that internucleosomal DNA fragmentation, characteristic of apoptosis and induced by ionizing radiation, is accompanied by concomitant decreases in Bcl-2 and Bcl-X mRNA levels in HL-60 and U-937 human leukemia cells. Apoptotic DNA fragmentation after exposure to TNF-alpha and C2-ceramide was also associated with down-regulation of Bcl-2 mRNA in HL-60 and U-937 cells, while Bcl-X mRNA production was unaffected. These results suggest that modulation of Bcl-2 gene expression may be a target for ceramide-mediated apoptosis following exposure to ionizing radiation and TNF-alpha. Changes in Bcl-2 expression may be the basis for the interactive killing observed between radiation and TNF-alpha in some human and tumor cells.
最近的研究表明，肿瘤坏死因子α（TNF-α）和电离辐射通过激活鞘磷脂水解为神经酰胺来诱导细胞凋亡。Bcl-2和相关基因Bcl-X可抑制多种形式的细胞凋亡。在此，我们报道，在HL-60和U-937人白血病细胞中，电离辐射诱导的、具有凋亡特征的核小体间DNA片段化，伴随着Bcl-2和Bcl-X mRNA水平的同时降低。HL-60和U-937细胞暴露于TNF-α和C2-神经酰胺后出现的凋亡性DNA片段化，也与Bcl-2 mRNA的下调有关，而Bcl-X mRNA的产生未受影响。这些结果表明，Bcl-2基因表达的调节可能是暴露于电离辐射和TNF-α后神经酰胺介导的细胞凋亡的一个靶点。Bcl-2表达的变化可能是某些人类肿瘤细胞中观察到的辐射与TNF-α之间协同杀伤作用的基础。
