Terman Alexei, Neuzil Jiri, Kågedal Katarina, Ollinger Karin, Brunk Ulf T
Division of Pathology II, Linköping University, Linköping, 58185, Sweden.
Exp Cell Res. 2002 Mar 10;274(1):9-15. doi: 10.1006/excr.2001.5441.
To better understand the role of lysosomes in apoptosis, we compared the responses to apoptotic stimuli of normal fibroblasts with those of inclusion cells (I-cells), i.e., fibroblasts with impaired function of lysosomal enzymes due to their missorting and ensuing nonlysosomal localization. Although both cell types did undergo apoptosis when exposed to the lysosomotropic detergent MSDH, the redox-cycling quinone naphthazarin, or the protein kinase inhibitor staurosporine, I-cells exerted a markedly decreased response to these agonists than did normal fibroblasts. Furthermore, leupeptin and pepstatin A (inhibitors of cysteine and aspartic proteases, respectively) suppressed staurosporine-induced apoptosis of normal fibroblasts, whereas survival of I-cells was unaffected. These findings give further support for the involvement of lysosomal enzymes in apoptosis and suggest I-cells as a suitable model for studying the role of lysosomes in programmed cell death.
为了更好地理解溶酶体在细胞凋亡中的作用，我们比较了正常成纤维细胞与包涵体细胞（I细胞）对凋亡刺激的反应，即由于溶酶体酶分选错误及其随后的非溶酶体定位而导致溶酶体酶功能受损的成纤维细胞。尽管当暴露于溶酶体促渗剂MSDH、氧化还原循环醌萘azarin或蛋白激酶抑制剂星形孢菌素时，两种细胞类型都确实发生了细胞凋亡，但I细胞对这些激动剂的反应明显低于正常成纤维细胞。此外，亮抑酶肽和胃蛋白酶抑制剂A（分别为半胱氨酸和天冬氨酸蛋白酶的抑制剂）抑制了星形孢菌素诱导的正常成纤维细胞凋亡，而I细胞的存活未受影响。这些发现进一步支持了溶酶体酶参与细胞凋亡，并表明I细胞是研究溶酶体在程序性细胞死亡中作用的合适模型。
