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PMID: 12021257 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Cyclosporin A inhibits caspase-independent death of NGF-deprived sympathetic neurons: a potential role for mitochondrial permeability transition.

The Journal of cell biology ·Vol. 157 ·No. 5 ·2002-05-27 ·Pages 771-81

Chang LK, Johnson EM

Abstract

Opening of the permeability transition pore (PTP) has been implicated as an important mitochondrial event that occurs during apoptosis. We examined the role of the PTP in the well-characterized cell death of rat sympathetic neurons deprived of nerve growth factor (NGF) in vitro. Removal of NGF causes these neurons to undergo either a classic apoptotic cell death or, when treated with a broad-spectrum caspase inhibitor such as boc-aspartyl(OMe)-fluoromethylketone (BAF), a delayed, nonapoptotic cell death. The PTP inhibitor, cyclosporin A (CsA), blocked commitment-to-die in the presence of BAF, as defined by the ability of NGF readdition to rescue cells, but had little effect on commitment-to-die in the absence of BAF. CsA did not have trophic effects on BAF-saved cells, but did block the decrease in mitochondrial membrane potential. These data suggest that PTP opening is a critical event in caspase-independent, nonapoptotic (but not caspase-dependent, apoptotic) death of NGF-deprived rat sympathetic neurons.

MeSH Terms
Animals Apoptosis/drug effects,physiology Calcineurin Inhibitors Caspase Inhibitors Caspases/metabolism Cell Membrane Permeability/drug effects,physiology Cells, Cultured Cyclosporine/pharmacology Enzyme Inhibitors/pharmacology Female Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Inbred ICR Mitochondria/metabolism Nerve Growth Factor/pharmacology Neurons/cytology,drug effects,metabolism Pregnancy Rats Rats, Sprague-Dawley Superior Cervical Ganglion/cytology
Chemicals
Calcineurin Inhibitors Caspase Inhibitors Enzyme Inhibitors Cyclosporine Nerve Growth Factor Caspases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Chang Louis K
Washington University School of Medicine, St. Louis, MO 63110, USA.
Johnson Eugene M
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200112130
Published
2002-05-27
Epub
2002-00-20
Pages
771-81
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2173417
Subset
IM
Grants
NIA NIH HHS · AG 12957 · United States
NINDS NIH HHS · NS 38651 · United States
External Links
PubMed source DOI: 10.1083/jcb.200112130 PMC Full Text View journal details
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