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Lysosomal membrane permeabilization causes oxidative stress and ferritin induction in macrophages
Author(s) -
Ghosh Moumita,
Carlsson Fredrik,
Laskar Amit,
Yuan Xi-Ming,
Li Wei
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.12.043
Subject(s) - oxidative stress , ferritin , programmed cell death , microbiology and biotechnology , cathepsin , apoptosis , chemistry , cathepsin d , mitochondrion , cathepsin b , biochemistry , oxidative phosphorylation , biology , enzyme
Moderate lysosomal membrane permeabilization (LMP) is an important inducer of apoptosis. Macrophages are professional scavengers and are rich in hydrolytic enzymes and iron. In the present study, we found that LMP by lysosomotropic detergent MSDH resulted in early up‐regulation of lysosomal cathepsins, oxidative stress and ferritin up‐regulation, and cell death. Lysosomotropic base NH 4 Cl reduced the ferritin induction and oxidative stress in apoptotic cells induced by MSDH. Cysteine cathepsin inhibitors significantly protected cell death and oxidative stress, but had less effect on ferritin induction. We conclude that oxidative stress induced by lysosomal rupture causes ferritin induction with concomitant mitochondrial damage, which are the potential target for prevention of cellular oxidative stress and cell death induced by typical lysosomotropic substances in different disorders.