The DOI matches its Crossref record.
Activation of the caspase-3 apoptotic cascade in traumatic spinal cord injury
Abstract
Traumatic spinal cord injury often results in complete loss of voluntary motor and sensory function below the site of injury. The long-term neurological deficits after spinal cord trauma may be due in part to widespread apoptosis of neurons and oligodendroglia in regions distant from and relatively unaffected by the initial injury. The caspase family of cysteine proteases regulates the execution of the mammalian apoptotic cell death program. Caspase-3 cleaves several essential downstream substrates involved in the expression of the apoptotic phenotype in vitro, including gelsolin, PAK2, fodrin, nuclear lamins and the inhibitory subunit of DNA fragmentation factor. Caspase-3 activation in vitro can be triggered by upstream events, leading to the release of cytochrome c from the mitochondria and the subsequent transactivation of procaspase-9 by Apaf-1. We report here that these upstream and downstream components of the caspase-3 apoptotic pathway are activated after traumatic spinal cord injury in rats, and occur early in neurons in the injury site and hours to days later in oligodendroglia adjacent to and distant from the injury site. Given these findings, targeting the upstream events of the caspase-3 cascade has therapeutic potential in the treatment of acute traumatic injury to the spinal cord.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“CASP-3 and CASP-7 are cysteine-aspartic acid proteases which, upon activation, execute the apoptotic program and play a central role in the extension of apoptosis after SCI [73,74]”
From MicroRNA-138-5p Targets Pro-Apoptotic Factors and Favors Neural Cell Survival: Analysis in the Injured Spinal Cord (2022) · cites this paper as [74]
Citations
Cites
No references could be resolved yet.
Research works printed but not linked: 25
- Shuman, S.L., Bresnahan, J.C. & Beattie, M.S. Apoptosis of microglia and oligodendrocytes after spinal cord contusion in rats. J. Neurosci. Res. 50 , 798–808 (1997). · DOI
- Liu, X.Z., et al. Neuronal and glial apoptosis after traumatic spinal cord injury. J. Neurosci. 17, 5395– 5406 (1997). · DOI · Paper page
- Crowe, M.J., Bresnahan, J.C., Shuman, S.L., Masters, J.N. & Beattie, M.S. Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys. Nature Med. 3, 73–76 (1997). · DOI · Paper page
- Emery, E. et al. Apoptosis after traumatic human spinal cord injury. J. Neurosurg. 89, 911–20 (1998). · DOI
- Cohen, G.M. Caspases: the executioners of apoptosis. Biochem. J. 326, 1–16 (1997). · DOI
- Salvesen, G.S. & Dixit, V.M. Caspases: intracellular signaling by proteolysis. Cell 91, 443– 6 (1997). · DOI
- Thornberry, N.A. The caspase family of cysteine proteases. Br. Med. Bull. 53, 478–490 (1997). · DOI
- Enari, M. et al. A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature 391, 43– 50 (1998). · DOI
- Sakahira, H., Enari, M. & Nagata, S. Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis. Nature 391, 96– 99 (1998). · DOI
- Rudel, T. & Bokoch, G.M. Membrane and morphological changes in apoptotic cells regulated by caspase-mediated activation of PAK2. Science 276, 1571–1574 ( 1997). · DOI
- Kluck, R.M., Bossy-Wetzel, E., Green, D.R. & Newmeyer, D.D. The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 275, 1132– 1136 (1997). · DOI
- Kothakota, S. et al. Caspase-3-generated fragment of gelsolin: effector of morphological change in apoptosis. Science 278, 294– 298 (1997). · DOI
- Pan, G., Humke, E.W. & Dixit, V.M. Activation of caspases triggered by cytochrome c in vitro. FEBS. Lett. 426, 151– 154 (1998). · DOI
- Hu, Y., Ding, L., Spencer, D.M. & Nunez, G. WD-40 repeat region regulates Apaf-1 self-association and procaspase-9 activation. J. Biol. Chem. 273, 33489–33494 (1998). · DOI
- Li, P. et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91, 479–489 (1997). · DOI · Paper page
- Liu, X., Kim, C.N., Yang, J., Jemmerson, R. & Wang, X. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86, 147–157 (1996). · DOI · Paper page
- Leoni, L.M. et al. Induction of an apoptotic program in cell-free extracts by 2-chloro-2'- deoxyadenosine 5´-triphosphate and cytochrome c. Proc. Natl. Acad. Sci. USA 95, 9567– 9571 (1998). · DOI
- Liu, X., Zou, H., Slaughter, C. & Wang, X. DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis. Cell 89, 175– 184 (1997). · DOI
- Liu, X. et al. The 40-kDa subunit of DNA fragmentation factor induces DNA fragmentation and chromatin condensation during apoptosis. Proc. Natl. Acad. Sci. USA 95, 8461–8466 ( 1998). · DOI
- Tang, D. & Kidd, V.J. Cleavage of DFF-45/ICAD by multiple caspases is essential for its function during apoptosis. J. Biol. Chem. 273, 28549–28552 ( 1998). · DOI
- Yakovlev, A.G., et al. Activation of CPP32-like caspases contributes to neuronal apoptosis and neurological dysfunction after traumatic brain injury. J. Neurosci. 17, 7415–7424 (1997). · DOI
- Pike, B.R. et al. Regional calpain and caspase-3 proteolysis of alpha-spectrin after traumatic brain injury. Neuroreport 9, 2437–2442 (1998). · DOI
- Namura, S. et al. Activation and cleavage of caspase-3 in apoptosis induced by experimental cerebral ischemia. J. Neurosci. 18, 3659–3668 (1998). · DOI
- Gruner, J. A monitored contusion model of spinal cord injury in the rat. J. Neurotrauma 9, 123–128 (1992). · DOI
- Basso, D., Beattie, M. & Breshnahan, J. Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection. Exp. Neurol. 139, 244–256 (1996). · DOI · Paper page
Cited by
Sorted by citations
Apoptosis in neurodegenerative disorders
Mattson, M. P. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35040009 · Cited by 1,605
Minocycline and Neurodegenerative Diseases
Kim, H.-S., & Suh, Y.-H. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.09.040 · Cited by 447
Chapter 4 Cell death in models of spinal cord injury
Beattie, M. S., Hermann, G. E., Rogers, R. C., & Bresnahan, J. C. (2002) · Progress in Brain Research · doi:10.1016/s0079-6123(02)37006-7 · Cited by 453
Rong, Y., Liu, W., Wang, J., Fan, J., Luo, Y., Li, L., Kong, F., Chen, J., Tang, P., & Cai, W. (2019) · Cell Death & Disease · doi:10.1038/s41419-019-1571-8 · Cited by 333
Temporal–Spatial Pattern of Acute Neuronal and Glial Loss after Spinal Cord Contusion
Grossman, S. D., Rosenberg, L. J., & Wrathall, J. R. (2001) · Experimental Neurology · doi:10.1006/exnr.2001.7628 · Cited by 310
Metadata
- Authors
- Springer, J. E., Azbill, R. D., & Knapp, P. E.
- Venue
- Nature Medicine
- Published
- 1999-08
- Volume
- 5
- Issue
- 8
- Pages
- 943-946
- ISSN
- 1078-8956
- 1546-170X
- Cited by
- 371
- References
- 0
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Activation of the caspase-3 apoptotic cascade in traumatic spinal cord injury. https://app.cochat.ai/papers/10.1038/11387
- The paper
- Springer, J. E., Azbill, R. D., & Knapp, P. E. (1999). Activation of the caspase-3 apoptotic cascade in traumatic spinal cord injury. Nature Medicine. https://doi.org/10.1038/11387