a Department of Pathology II, Faculty of Health Sciences , Linköping University , Linköping , Sweden.
Redox Rep. 1997 Feb;3(1):65-70. doi: 10.1080/13510002.1997.11747092.
When macrophage-like J-774 cells are subjected to limited oxidative stress, such as exposure to hydrogen peroxide in a moderate bolus dose, some of their lysosomes rupture-as here assayed by the acridine orange relocalization test-secondary to intralysosomal, iron-catalysed, oxidative reactions. The resultant leakage into the cytosol of hydrolytic enzymes, such as cathepsin-D (as shown here), may initiate a slow degradation/fragmentation process of an apoptotic type within cells still having intact plasma membranes. In contrast, severe oxidative stress also results in extensive lysosomal rupture but leads to necrosis. The chelation of (normally occurring) intralysosomal low-molecular weight iron, by endocytotic uptake of desferrioxamine, largely prevents oxidative stress-induced apoptosis whereas lysosomal iron-loading, by endocytotic uptake of complexed ferric iron, considerably enhances the process. We conclude that oxidant-mediated and iron-catalysed lysosomal rupture leads to decompartmentalization of lysosomal enzymes which in turn may initiate and promote the apoptotic process.
当巨噬细胞样 J-774 细胞受到有限的氧化应激时，例如暴露于中等剂量的过氧化氢中，它们的一些溶酶体就会破裂——如这里通过吖啶橙重定位试验所测定的——这是由于溶酶体内铁催化的氧化反应。结果，水解酶（如组织蛋白酶 D，如图所示）漏入细胞质，可能会在仍然具有完整质膜的细胞内引发一种缓慢的凋亡样降解/碎裂过程。相比之下，严重的氧化应激也会导致广泛的溶酶体破裂，但会导致坏死。通过内吞摄取去铁胺螯合（通常存在于）溶酶体内的低分子量铁，在很大程度上可以防止氧化应激诱导的细胞凋亡，而通过内吞摄取铁复合物使溶酶体铁超载，则会大大增强这一过程。我们的结论是，氧化剂介导和铁催化的溶酶体破裂导致溶酶体酶的去区室化，进而可能引发并促进细胞凋亡过程。
