Journal
AUTOPHAGY
Volume 2, Issue 3, Pages 228-230Publisher
LANDES BIOSCIENCE
DOI: 10.4161/auto.2703
Keywords
autophagy; apoptosis; bafilomycin
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Funding
- PHS HHS [35107] Funding Source: Medline
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Bafilomycin Al (BafAl), which is a member of the plecomacrolide sub-class of macrolide antibiotics, has differential, concentration-dependent effects on neuronal cell viability. When used at high concentrations, BafAl inhibits vacuolar ATPase (V-ATPase), promotes the accumulation of autophagic vacuoles and triggers Bax-dependent apoptosis. These effects are similar to those induced by the lysosomotropic agent chloroquine. Conversely, at concentrations below its reported ability to completely inhibit V-ATPase, BafAl dramatically attenuates chloroquine-induced apoptosis. The protective effects of BafAl appear to be independent of the chloroquine-induced accumulation of autophagosomes. Rather, BafAl appears to inhibit events downstream of chloroquine-induced autophagosome accumulation, such as the loss of mitochondrial or lysosomal integrity. Our finding that BafAl inhibits the death of neurons induced by autophagic stress/inhibition suggests a potentially novel mechanism of action apart from its ability to inhibit V-ATPase. Here we provide further evidence of neuroprotection against chloroquine-induced death by plecomacrolide antibiotics that are structurally similar to BafAl, including bafilomycin Bl and concanamycin A, and discuss potential mechanism(s) of neuroprotection against autophagic stress.
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