Dale G L, Daniels R B, Beckman J, Norenberg S L
Department of Molecular and Experimental Medicine, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Adv Exp Med Biol. 1991;307:93-103. doi: 10.1007/978-1-4684-5985-2_9.
The above data continue to demonstrate the metabolic well being of the aged red cell as it is isolated from rabbits. The abundance of ATP, the absence of surface-bound IgG and a variety of other observations at this time lead to the tentative conclusion that the senescent red cell is amazingly healthy. Many investigators have predicted that the red cell is removed from the circulation as a metabolically exhausted effete cell. There is currently no evidence to support this other than a decrease in deformability of the cells with time, but it is not clear that this decline in deformability is sufficient to keep the cell from circulating. In either case, many of the previously proposed causes of cellular removal are clearly incorrect for the rabbit, and it is now time to focus on new directions for observing either cellular impairment or perhaps the presence of a cellular clock which is independent of the cell's metabolic state. Another point which should be addressed is the reliability of the biotinylation model in rabbits as it relates to red cells in other species. So far several observations in aged red cells isolated with valid models have been reproduced across species boundaries including the rise in ATP, the fall in AMP deaminase activity, the shift in the 4.1a to 4.1b protein ratio, the stability of a number of glycolytic enzymes, and the instability of pyrimidine 5'-nucleotidase activity. To this point, the rabbit has been a reliable model of red cell aging and one with implications for other species.
上述数据继续证明了从兔子体内分离出的衰老红细胞的代谢健康状况。此时,丰富的三磷酸腺苷(ATP)、表面结合免疫球蛋白G(IgG)的缺失以及其他各种观察结果,得出了一个初步结论:衰老红细胞惊人地健康。许多研究人员曾预测,红细胞作为代谢耗尽的衰老细胞从循环中被清除。目前除了细胞随着时间推移可变形性降低外,没有证据支持这一点,但尚不清楚这种可变形性的下降是否足以阻止细胞在循环中流动。无论哪种情况,许多先前提出的细胞清除原因对于兔子来说显然是不正确的,现在是时候关注观察细胞损伤或可能存在的与细胞代谢状态无关的细胞时钟的新方向了。另一个需要解决的问题是兔子中生物素化模型与其他物种红细胞的相关性的可靠性。到目前为止,在通过有效模型分离的衰老红细胞中的一些观察结果已跨越物种界限得到重现,包括ATP的增加、AMP脱氨酶活性的下降、4.1a与4.1b蛋白比例的变化、多种糖酵解酶的稳定性以及嘧啶5'-核苷酸酶活性的不稳定性。至此,兔子一直是红细胞衰老的可靠模型,并且对其他物种具有启示意义。