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Lysosomal and mitochondrial pathways in H 2 O 2 ‐induced apoptosis of alveolar type II cells
Author(s) -
Yin Lei,
Stearns Rebecca,
GonzálezFlecha Beatriz
Publication year - 2004
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20277
Subject(s) - apoptosis , microbiology and biotechnology , pepstatin , cathepsin d , cytochrome c , cathepsin b , programmed cell death , mitochondrion , cathepsin , chemistry , caspase , intracellular , biology , biochemistry , enzyme , protease
Increasing evidence suggests a role for apoptosis in the maintenance of the alveolar epithelium under normal and pathological conditions. However, the signaling pathways modulating alveolar type II (AT II) cell apoptosis remain poorly defined. Here we investigated the role of lysosomes as modulators of oxidant‐mediated AT II cell apoptosis using an in vitro model of H 2 O 2 ‐stress. H 2 O 2 stress led to time‐dependent increases in intracellular oxidants, mitochondrial membrane polarization, cytochrome c release, lysosomal rupture, and AT II cells apoptosis. Increased apoptosis was prevented by specific inhibition of the caspase cascade using the broad‐spectrum caspase inhibitor z‐VAD‐fmk or a caspase 3 inhibitor, or by using functional inhibitors for cathepsin D (pepstatin A) or cathepsin B. Inhibition of cathepsin D also prevented mitochondrial permeabilization and cythocrome c release suggesting that lysosomal rupture precedes and is necessary for the activation of the mitochondrial pathway of cell death. © 2004 Wiley‐Liss, Inc.