DOI: 10.1083/jcb.150.1.131. Caspase Inhibition Extends the Commitment to Neuronal Death Beyond Cytochrome <i>c</i> Release to the Point of Mitochondrial Depolarization

Caspase Inhibition Extends the Commitment to Neuronal Death Beyond Cytochrome c Release to the Point of Mitochondrial Depolarization

10.1083/jcb.150.1.131

Crossref journal-article

Rockefeller University Press

The Journal of Cell Biology (291)

Abstract

Nerve growth factor (NGF) deprivation induces a Bax-dependent, caspase-dependent programmed cell death in sympathetic neurons. We examined whether the release of cytochrome c was accompanied by the loss of mitochondrial membrane potential during sympathetic neuronal death. NGF- deprived, caspase inhibitor–treated mouse sympathetic neurons maintained mitochondrial membrane poten-tial for 25–30 h after releasing cytochrome c. NGF- deprived sympathetic neurons became committed to die, as measured by the inability of cells to be rescued by NGF readdition, at the time of cytochrome c release. In the presence of caspase inhibitor, however, this commitment to death was extended beyond the point of cytochrome c release, but only up to the subsequent point of mitochondrial membrane potential loss. Caspase-9 deficiency also arrested NGF-deprived sympathetic neurons after release of cytochrome c, and permitted these neurons to be rescued with NGF readdition. Commitment to death in the NGF-deprived, caspase- 9–deficient sympathetic neurons was also coincident with the loss of mitochondrial membrane potential. Thus, caspase inhibition extended commitment to death in trophic factor–deprived sympathetic neurons and allowed recovery of neurons arrested after the loss of cytochrome c, but not beyond the subsequent loss of mitochondrial membrane potential.

Bibliography

Deshmukh, M., Kuida, K., & Johnson, E. M. (2000). Caspase Inhibition Extends the Commitment to Neuronal Death Beyond Cytochrome c Release to the Point of Mitochondrial Depolarization. The Journal of Cell Biology, 150(1), 131â144.

Authors 3

Mohanish Deshmukh (first)
Keisuke Kuida (additional)
Eugene M. Johnson (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:45 p.m.)
Deposited	2 years, 1 month ago (July 22, 2023, 7:09 a.m.)
Indexed	1 month, 3 weeks ago (July 7, 2025, 1:45 a.m.)
Issued	25 years, 1 month ago (July 10, 2000)
Published	25 years, 1 month ago (July 10, 2000)
Published Online	25 years, 1 month ago (July 10, 2000)
Published Print	25 years, 1 month ago (July 10, 2000)

Funders 0

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BibTeX

@article{Deshmukh_2000, title={Caspase Inhibition Extends the Commitment to Neuronal Death Beyond Cytochrome c Release to the Point of Mitochondrial Depolarization}, volume={150}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.150.1.131}, DOI={10.1083/jcb.150.1.131}, number={1}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Deshmukh, Mohanish and Kuida, Keisuke and Johnson, Eugene M.}, year={2000}, month=jul, pages={131–144} }

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