Nishishita K, Sakai H, Sakai E, Kato Y, Yamamoto K
Department of Pharmacology, Nagasaki University School of Dentistry, Japan.
Arch Biochem Biophys. 1996 Sep 15;333(2):349-58. doi: 10.1006/abbi.1996.0401.
Age-related and dexamethasone (DEX)-induced changes in the cellular levels, distributions, and molecular forms of two distinct intracellular aspartic proteinases, cathepsin E (CE) and cathepsin D (CD), were investigated in rat thymus and spleen by immunohistochemical and quantitative analyses. In the thymus, CE was predominantly restricted to thymocytes and macrophage-like cells, whereas CD was associated mainly with the stromal cells. The increased thymic CE level observed in young rats up to 8 weeks of age was markedly decreased in aged rats (78-80 weeks of age), in accordance with the involution of the thymus, while there was little difference in the thymic CD level between young and aged rats. Subcutaneous administration of DEX also caused a marked decrease of the thymic CE level in response to the depletion of thymocytes. In contrast, a great accumulation of CD occurred in the thymic stromal cells after DEX treatment. Immunoblotting analyses revealed that CE in thymocytes isolated from young rats consisted predominantly of a 46-kDa proform which was greatly converted into a 42-kDa mature form in DEX-treated thymocytes. This conversion, however, was scarcely observed during the normal aging process. In the spleen, CE was also abundant in macrophage-like cells and lymphocytes and its level was not significantly changed between young and aged rats. However, DEX treatment caused a marked decrease of the splenic CE and CD levels in accordance with the depletion of the white pulp. Among the lymphoid cell types examined, splenic B cells were the most abundant in CE. The CE level in thymocytes and splenic T-cells was more than twice that in circulating lymphocytes. We concluded that CE is related to the process of activation-induced lymphocyte depletion.
通过免疫组织化学和定量分析，研究了大鼠胸腺和脾脏中与年龄相关以及地塞米松（DEX）诱导的两种不同细胞内天冬氨酸蛋白酶组织蛋白酶E（CE）和组织蛋白酶D（CD）的细胞水平、分布和分子形式的变化。在胸腺中，CE主要局限于胸腺细胞和巨噬细胞样细胞，而CD主要与基质细胞相关。在8周龄以下的幼鼠中观察到的胸腺CE水平升高，在老年大鼠（78 - 80周龄）中随着胸腺退化而显著降低，而幼鼠和老年大鼠的胸腺CD水平差异不大。皮下注射DEX也会因胸腺细胞耗竭而导致胸腺CE水平显著降低。相反，DEX处理后胸腺基质细胞中CD大量积累。免疫印迹分析显示，从幼鼠分离的胸腺细胞中的CE主要由46 kDa的前体形式组成，在DEX处理的胸腺细胞中大量转化为42 kDa的成熟形式。然而，在正常衰老过程中几乎未观察到这种转化。在脾脏中，CE在巨噬细胞样细胞和淋巴细胞中也很丰富，其水平在幼鼠和老年大鼠之间没有显著变化。然而，DEX处理导致脾脏CE和CD水平随着白髓的耗竭而显著降低。在所检查的淋巴细胞类型中，脾脏B细胞中的CE最为丰富。胸腺细胞和脾脏T细胞中的CE水平是循环淋巴细胞中的两倍多。我们得出结论，CE与激活诱导的淋巴细胞耗竭过程有关。
