Krajewski S, Krajewska M, Shabaik A, Miyashita T, Wang H G, Reed J C
Oncogene and Tumor Suppressor Gene Program, La Jolla Cancer Research Foundation, California 92037.
Am J Pathol. 1994 Dec;145(6):1323-36.
The protein encoded by the bcl-2 gene is a regulator of programmed cell death and apoptosis. The cell survival-promoting activity of this protein is opposed by Bax, a homologous protein that forms heterodimers with Bcl-2 and accelerates rates of cell death. In this report, the in vivo patterns of bax gene expression were immunohistochemically assessed in the mouse, with a polyclonal antibody raised against a synthetic peptide corresponding to a unique region in the murine Bax protein. Direct comparisons were made with Bcl-2 by using anti-peptide antisera specific for the mouse Bcl-2 protein. The expression of bax was more widespread than bcl-2. For example, Bax immunoreactivity was present in the hepatocytes of the liver, the exocrine pancreas, and the renal tubule epithelial cells whereas Bcl-2 was absent from these tissues. Both the Bax and Bcl-2 proteins were present in several epithelia examined, including the small intestines, colon, breast, prostate, respiratory tract, and skin. The most intense Bax immunostaining was seen in cells located in the base of the crypts of the small intestinal mucosa, consistent with reports of high rates of spontaneous and inducible apoptosis in this region. Bcl-2 immunostaining was completely absent from these cells but was present in the absorptive epithelial cells of the small intestine. In contrast, Bax immunostaining in the colon tended to be stronger in the surface epithelial cells that had advanced up the crypts towards the lumen and that are destined for programmed cell death, whereas Bcl-2 immunoreactivity generally was stronger in the base of the colonic crypts. Similarly, bax expression in the gastric pits of the stomach occurred in a gradient such that higher levels of Bax immunostaining were found in the upper layers of gastric glands than in the lower regions. In addition, strong Bax immunostaining was detected in the androgen-dependent secretory epithelial cells of the prostate, whereas Bcl-2 was limited to the androgen-independent basal cells. Like Bcl-2, Bax was found in the thymic medulla but not the cortex, despite the propensity for immature cortical thymocytes to undergo apoptosis. Unlike Bcl-2, however, Bax immunostaining tended to be more intense in the germinal center lymphocytes of lymph nodes than in the interfollicular lymphocytes, consistent with the high rate of apoptotic cell death in the former.(ABSTRACT TRUNCATED AT 400 WORDS)
bcl - 2基因编码的蛋白质是程序性细胞死亡和凋亡的调节因子。该蛋白质促进细胞存活的活性受到Bax的拮抗，Bax是一种同源蛋白质，可与Bcl - 2形成异二聚体并加速细胞死亡速率。在本报告中，使用针对与小鼠Bax蛋白独特区域相对应的合成肽产生的多克隆抗体，通过免疫组织化学方法评估了小鼠体内bax基因的表达模式。通过使用针对小鼠Bcl - 2蛋白的抗肽抗血清与Bcl - 2进行直接比较。bax的表达比bcl - 2更广泛。例如，Bax免疫反应性存在于肝脏的肝细胞、外分泌胰腺和肾小管上皮细胞中，而这些组织中不存在Bcl - 2。在检查的几种上皮组织中都存在Bax和Bcl - 2蛋白，包括小肠、结肠、乳腺、前列腺、呼吸道和皮肤。在小肠黏膜隐窝底部的细胞中观察到最强的Bax免疫染色，这与该区域自发和诱导性凋亡率高的报道一致。这些细胞中完全没有Bcl - 2免疫染色，但在小肠的吸收性上皮细胞中存在。相反，结肠中的Bax免疫染色在沿着隐窝向上朝向管腔推进并注定要进行程序性细胞死亡的表面上皮细胞中往往更强，而Bcl - 2免疫反应性通常在结肠隐窝底部更强。同样，胃小凹中的bax表达呈梯度分布，使得胃腺上层的Bax免疫染色水平高于下层区域。此外，在前列腺的雄激素依赖性分泌上皮细胞中检测到强烈的Bax免疫染色，而Bcl - 2仅限于雄激素非依赖性基底细胞。与Bcl - 2一样，尽管未成熟的皮质胸腺细胞有发生凋亡的倾向，但Bax在胸腺髓质中被发现，而在皮质中未发现。然而，与Bcl - 2不同的是，Bax免疫染色在淋巴结生发中心淋巴细胞中往往比滤泡间淋巴细胞中更强，这与前者中凋亡细胞死亡的高发生率一致。（摘要截取自400字）
