Cell death induced by peroxidized low-density lipoprotein: endopepsis.
Peroxidized low-density lipoprotein (p-LDL) has been previously demonstrated to be preferentially cytotoxic to certain malignant cells compared to normal cells of the same type. We present evidence that p-LDL is at least partially taken up through the LDL receptor and that it becomes localized in lysosomes. The integrity of lysosomes of p-LDL-treated cells is compromised, and leakage of their contents into the cytosol occurs. This leakage occurs early and precedes mitochondrial dysfunction. Brefeldin A inhibits this leakage, perhaps by interfering with the traffic between endosomes and lysosomes. Electron micrographs taken at various times suggest a mechanism of cell death which resembles certain aspects of the broad definition of apoptosis. However, we suggest that the cell death observed following p-LDL-induced release of lysosomal contents is essentially unique, with released lysosomal enzymes degrading the cell from within. We suggest that this process should be described as endopepsis.
Fossel
E T
ET
Department of Radiology, Beth Israel Hospital, Boston, MA 02215.
Zanella
C L
CL
Fletcher
J G
JG
Hui
K K
KK
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000648:ultrastructure; D020126:Brefeldin A; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D003517:Cyclopentanes / Q000494:pharmacology; D004357:Drug Synergism; D010450:Endopeptidases / Q000502:physiology*; D005354:Fibrosarcoma / Q000188:drug therapy / Q000473:pathology / Q000648:ultrastructure; D006615:Hip / Q000473:pathology; D006801:Humans; D006867:Hydrolases / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000633:toxicity*; D008247:Lysosomes / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology*; D010545:Peroxides / Q000633:toxicity*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000648:ultrastructure; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011973:Receptors, LDL / Q000378:metabolism; D014407:Tumor Cells, Cultured
D003517:Cyclopentanes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D010545:Peroxides; D011500:Protein Synthesis Inhibitors; D011973:Receptors, LDL; D020126:Brefeldin A; D006867:Hydrolases; D010450:Endopeptidases