Immunohistochemical determination of in vivo distribution of Bax, a dominant inhibitor of Bcl-2.
Immunohistochemical determination of in vivo distribution of Bax, a dominant inhibitor of Bcl-2.
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发表时间：
1994-12
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通讯作者：
S. Krajewski;M. Krajewska;A. Shabaik;T. Miyashita;H. G. Wang;John Calvin Reed
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作者：
S. Krajewski;M. Krajewska;A. Shabaik;T. Miyashita;H. G. Wang;John Calvin Reed
bcl-2 基因编码的蛋白质是程序性细胞死亡和细胞凋亡的调节因子。该蛋白的细胞存活促进活性与 Bax 相反，Bax 是一种同源蛋白，可与 Bcl-2 形成异二聚体并加速细胞死亡速度。在本报告中，使用针对与鼠 Bax 蛋白中的独特区域相对应的合成肽的多克隆抗体，对小鼠体内的 bax 基因表达模式进行了免疫组织化学评估。通过使用小鼠 Bcl-2 蛋白特异性的抗肽抗血清与 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 Bcl-2 在这些组织中不存在。 Bax 和 Bcl-2 蛋白均存在于所检查的几种上皮细胞中，包括小肠、结肠、乳房、前列腺、呼吸道和皮肤。最强烈的 Bax 免疫染色出现在位于小肠粘膜隐窝底部的细胞中，这与该区域自发性和诱导性细胞凋亡高发生率的报道一致。这些细胞完全不存在 Bcl-2 免疫染色，但存在于小肠的吸收性上皮细胞中。相比之下，结肠中的 Bax 免疫染色往往在表面上皮细胞中更强，这些细胞已经沿着隐窝向内腔前进，并且注定会发生程序性细胞死亡，而 Bcl-2 免疫反应性通常在结肠隐窝基部更强。类似地，胃胃凹中的bax表达呈梯度，使得胃腺上层的Bax免疫染色水平高于下层区域。此外，在前列腺雄激素依赖性分泌上皮细胞中检测到强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，Bax 存在于胸腺髓质而非皮质中，尽管未成熟的皮质胸腺细胞有发生凋亡的倾向。然而，与 Bcl-2 不同的是，Bax 免疫染色在淋巴结的生发中心淋巴细胞中比在滤泡间淋巴细胞中更强烈，这与前者的高凋亡细胞死亡率一致。（摘要截断为 400 字）
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)