A Bax-Induced Pro-Oxidant State Is Critical for Cytochrome c Release during Programmed Neuronal Death
Open accessAbstract
Bax is required for the apoptotic death of sympathetic neurons deprived of nerve growth factor (NGF). After NGF withdrawal, Bax translocates from the cytoplasm to the mitochondria of these cells and induces release of the proapoptotic protein cytochrome c. Here, we report that withdrawing NGF from mouse sympathetic neurons caused an increase of mitochondria-derived reactive oxygen species (ROS). Suppressing these ROS inhibited apoptosis. Bax deletion blocked death and prevented the ROS burst. Inducing a pro-oxidant state similar to that in NGF-deprived, wild-type cells caused cytochrome c release even in neurons lacking Bax. A similar ROS burst in cerebellar granule neurons undergoing apoptosis was also blocked by Bax deletion. These findings indicate that Bax lies upstream from increased ROS in NGF-deprived neurons and suggest that the Bax-induced ROS burst is both necessary and sufficient for cytochrome c redistribution in these cells.
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CM-H2DCFDA is trapped in neurons, is insensitive to pH changes within the physiological range, and is not photo-oxidized by the laser power and exposure time used in these experiments.
“This characterization shows that CM-H2DCFDA is trapped in neurons, is insensitive to pH changes within the physiological range, and is not photo-oxidized by the laser power and exposure time used in these experiments.”
From The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease (2011) · cites this paper as Kirkland et al., 2002
The ROS measurement section (page not specified) says CM-H2DCFDA is trapped in cells and reports little dye leakage from neurons. It does not establish that the dye is insensitive to physiological pH changes or that the laser power and exposure time used prevent photo-oxidation; searches for those properties found only the microscopy settings. (LLM, conf=0.86)
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Research works printed but not linked: 1
- Halliwell B, Gutteridge JMC (1999) Free radicals in biology and medi- cine, Ed 3. Oxford: Oxford UP.
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McManus, M. J., Murphy, M. P., & Franklin, J. L. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.0552-11.2011 · Cited by 432 · see citing works
Self-citationHuai, J., Vögtle, F.-N., Jöckel, L., Li, Y., Kiefer, T., Ricci, J.-E., & Borner, C. (2013) · Journal of Cell Science · doi:10.1242/jcs.129999 · Cited by 43 · see citing works
- Authors
- Kirkland, R. A., Windelborn, J. A., Kasprzak, J. M., & Franklin, J. L.
- Affiliations
- University of Wisconsin–Madison (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2002-08-01
- Volume
- 22
- Issue
- 15
- Pages
- 6480-6490
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6758153
- OpenAlex
- W2149065933
- Cited by
- 165
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 3 · 2021: 7 · 2020: 9 · 2019: 4 · 2018: 3 · 2017: 7 · 2016: 9 · 2015: 6 · 2014: 4 · 2013: 10 · 2012: 6
- FWCI
- 4.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (NS37110)
- National Institute of Neurological Disorders and Stroke (R29NS037110, R01NS037110)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- Bax, cytochrome c release, reactive oxygen species, mitochondrial reactive oxygen species, apoptosis, nerve growth factor withdrawal, sympathetic neurons, cerebellar granule cells
- MeSH terms
- Animals, Cells, Cultured, Cerebellum, Cytochrome c Group, Electron Transport, Fluorescent Dyes, Heterozygote, Homozygote, Hydrogen Peroxide, Immunohistochemistry, Mitochondria, Neurons, Oxidation-Reduction, Proto-Oncogene Proteins, Uncoupling Agents, Oxidants, Apoptosis, Reactive Oxygen Species, Superior Cervical Ganglion, Mice, Knockout, Proto-Oncogene Proteins c-bcl-2, Nerve Growth Factor, bcl-2-Associated X Protein, Mice
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