Institute of Nutrition, Department of Nutritional Toxicology, Friedrich Schiller University Jena, 07743 Jena, Germany.
Free Radic Biol Med. 2011 Mar 1;50(5):585-91. doi: 10.1016/j.freeradbiomed.2010.12.011. Epub 2010 Dec 16.
Lipofuscin, a highly oxidized aggregate, consists of covalently cross-linked proteins, lipids, and sugar residues and is one of the major life-span-limiting factors in postmitotic aging cells. An artificial model of this material, showing characteristics and effects comparable to those of the natural form, has turned out to be very useful for in vitro studies. Artificial lipofuscin was used to investigate its effects on the viability of human fibroblasts, its rate of uptake, and its ability to inhibit the proteasomal system. The inhibition of the proteasomal system is one of the major aspects of the cytotoxic effects of lipofuscin. We present here that this proteasomal inhibition is due to proteasomal binding to the lipofuscin surface motifs, degradable by protease K. Furthermore, removal of the surface peptide structures by protease K strongly reduces the cytotoxic effects of lipofuscin and binding of cellular proteins and proteasomes to intracellular protein aggregates.
脂褐素是一种高度氧化的聚集物，由共价交联的蛋白质、脂质和糖残基组成，是有丝分裂后衰老细胞中主要的寿命限制因素之一。这种物质的人工模型显示出与天然形式相当的特性和效果，对于体外研究非常有用。人工脂褐素被用于研究其对人成纤维细胞活力、摄取率以及抑制蛋白酶体系统能力的影响。蛋白酶体系统的抑制是脂褐素细胞毒性作用的主要方面之一。我们在这里提出，这种蛋白酶体抑制是由于蛋白酶体与脂褐素表面基序结合，可被蛋白酶 K 降解。此外，蛋白酶 K 去除表面肽结构可强烈降低脂褐素的细胞毒性作用，并减少细胞内蛋白质和蛋白酶体与细胞内蛋白质聚集体的结合。
