An elevated bax/bcl-2 ratio corresponds with the onset of prostate epithelial cell apoptosis
An elevated bax/bcl-2 ratio corresponds with the onset of prostate epithelial cell apoptosis
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DOI：
10.1038/sj.cdd.4400453
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发表时间：
1999-01-01
影响因子：
12.4
通讯作者：
Buttyan, R
中科院分区：
文献类型：
--
作者：
Perlman, H;Zhang, XJ;Buttyan, R
成年雄性大鼠的前列腺高度依赖雄性激素。阉割通过一个涉及绝大多数细胞凋亡损失的过程启动了该组织的退化。我们研究了这种具有良好特征的体内细胞凋亡模型，以评估两个特定基因产物bcl-2和bax的表达如何受到去势的影响，这两个基因产物已知对细胞凋亡的调节很重要。一项RNase保护实验显示，bax mRNA的表达在去势后短暂升高，在第3天达到峰值，随后下降。相比之下，bcl-2 mRNA的表达在去势后的7天内持续升高。通过对退化的大鼠腹侧前列腺组织进行原位杂交分析，证实了编码这两个基因的mrna表达的明显变化。mrna的升高明显局限于腺体的分泌性上皮细胞，这是受去势影响最大的组织的细胞室。最后，使用bax和bcl-2特异性抗体对退化大鼠前列腺中bax和bcl-2蛋白的表达进行SDS - PAGE/Western blot分析，结果显示bax和bcl-2蛋白水平的变化与mrna的变化相似且一致。综上所述，bax和bcl-2基因产物的表达在阉割诱导的大鼠腹侧前列腺退化过程中受到独特的调节。我们观察到的变化表明，组织中bax/bcl-2表达比在去势后的第2天和第3天达到峰值，与前列腺细胞凋亡的高峰期相吻合。这些数据支持先前在体外系统中进行的研究，其中表明bax/bcl-2比率决定细胞的凋亡潜力。
The prostate gland in adult male rats is highly dependent on androgenic steroids. Castration initiates the regression of this tissue through a process involving the loss of the vast majority of cells by means of apoptosis. We studied this well characterized in vivo model of apoptosis to evaluate how the expression of two particular gene products, bcl-2 and bax, known to be important for the regulation of apoptosis were affected by castration. An RNase protection assay designed to quantify the levels of bax mRNA showed that this transcript was transiently elevated after castration, reaching a peak in expression at3 days and declining thereafter. In contrast, bcl-2 mRNA expression was continuously elevated over a period of up to 7 days after castration. The distinct changes in the expression of the mRNAs encoding these two genes were confirmed by an in situ hybridization analysis of regressing rat ventral prostate tissues. The elevation in mRNAs were apparently restricted to the secretory epithelial cells of the gland, the cellular compartment of the tissue most affected by castration. Finally, SDS - PAGE/Western blot analysis of bax and bcl-2 protein expression in the regressing rat prostate gland with bax and bcl-2-specific antibodies showed that the changes in the bax and bcl-2 protein levels were similar and consistent to that found for the mRNAs. In summary, the expression of both bax and bcl-2 gene products are uniquely modulated during castration-induced regression of the rat ventral prostate gland. The changes we observed identify a transient but marked increase in the bax/bcl-2 expression ratio of the tissue that peaks on the second and third days after castration, coinciding with the peak periods of prostate cell apoptosis. These data support previous studies done on in vitro systems wherein it was shown that the bax/bcl-2 ratio determines the apoptotic potential of a cell.