Determinants of the apoptotic response to lysosomal photodamage.
Studies with mouse leukemia L1210 cells revealed that selective lysosomal photodamage caused by any of three photosensitizing agents was followed by a gradual loss of the mitochondrial membrane potential (delta psi m), release of cytochrome c into the cytosol, increased DEVDase activity (a measure of levels of caspase-3) and a limited apoptotic response. Similar effects were observed in the murine hepatoma 1c1c7 cell line. Immunofluorescence techniques employing 1c1c7 cells demonstrated the immediate release of the lysosomal enzyme cathepsin B following lysosomal photodamage. These studies suggest that the cytotoxic effects of lysosomal photodamage are initiated by released lysosomal proteases that either directly and/or indirectly activate caspases as a consequence of the induction of mitochondrial damage.
Kessel
D
D
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA. dhkessel@med.wayne.edu
Luo
Y
Y
Mathieu
P
P
Reiners
J J
JJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D002401:Cathepsin B / Q000032:analysis; D007425:Intracellular Membranes / Q000187:drug effects; D007939:Leukemia L1210; D008027:Light; D008114:Liver Neoplasms, Experimental; D008247:Lysosomes / Q000187:drug effects* / Q000201:enzymology / Q000528:radiation effects; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D017319:Photosensitizing Agents / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D017319:Photosensitizing Agents; D002401:Cathepsin B