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Article Addendum
Autophagy, Bafilomycin and Cell Death: The “A-B-Cs” of Plecomacrolide-Induced Neuroprotection
John J. Shacka, Barbara J. Klocke and Kevin A. Roth
volume 2 | issue 3
July/August/September 2006Pages: 228 - 230
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Bafilomycin A1 (BafA1), 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, BafA1 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, BafA1 dramatically attenuates chloroquine-induced apoptosis. The protective effects of BafA1 appear to be independent of the chloroquine-induced accumulation of autophagosomes. Rather, BafA1 appears to inhibit events downstream of chloroquine-induced autophagosome accumulation, such as the loss mitochondrial or lysosomal integrity. Our finding that BafA1 inhibits the death of neurons induced by autophagic stress 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 BafA1, including bafilomycin B1 and concanamycin A, and discuss potential mechanism(s) of neuroprotection against autophagic stress.
Addendum to:
Bafilomycin A1 Inhibits Chloroquine-Induced Death of Cerebellar Granule Neurons
John J. Shacka, Barbara J. Klocke, Masahiro Shibata, Yasuo Uchiyama, Geeta Datta, Robert E. Schmidt and Kevin A. Roth
Mol Pharmacol 2006; 69:1125-36
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.