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Rapid Upregulation of Caspase-3 in Rat Spinal Cord after Injury: mRNA, Protein, and Cellular Localization Correlates with Apoptotic Cell Death

Citron, Bruce A., Arnold, Paul M., Sebastian, Cyril, Qin, Fan, Malladi, Sundaravalli, Ameenuddin, Syed, Landis, Mary E., Festoff, Barry W.·2000·Experimental Neurology
DOI 10.1006/exnr.2000.7523
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Abstract

Although the precise mechanisms explaining loss of, and failure to regain, function after spinal cord injury are unknown, there is increasing interest in the role of "secondary cell death." One prevalent theme in cell loss in other regions of the CNS involves apoptosis executed by the intracellular caspase proteases. A recent study demonstrated that spinal cord injury rapidly increased the activation of caspase-3. Our previous studies demonstrated peak apoptosis in three of four cellular compartments 3 days after controlled contusion in the rat. We have extended these analyses to include enzyme and substrate studies of caspase subfamilies both in rostral and in caudal adjacent segments compared to the lesion site. Although presumed activation of programmed proenzyme is considered the mechanism for enhanced caspases, our novel analyses were designed to detect upregulation of gene expression. We surveyed traumatically injured spinal cord for caspase family messages with a modified differential mRNA display approach and found that the caspase-3 (CASP3) message was present and upregulated severalfold after injury. Our results clearly demonstrate that cell death in the spinal cord occurs after posttranslational activation of caspases that follow, at least for caspase-3, initial upregulation of CASP3 mRNA levels.

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Research works printed but not linked: 66

  1. Alnemri, 1996, Human ICE/CED 3 protease nomenclature, Cell, 87, 171, 10.1016/S0092-8674(00)81334-3 · DOI
  2. Armstrong, 1997, Activation of the CED3/ICE related protease CPP32 in cerebellar granule neurons undergoing apoptosis but not necrosis, J. Neurosci., 17, 553, 10.1523/JNEUROSCI.17-02-00553.1997 · DOI
  3. Arnold, 2000, Caspase-3 inhibition is neuroprotective after spinal cord injury, J. Neurochem. (Suppl.), 74, S73
  4. Asahi, 1997, Expression of interleukin-1 beta converting enzyme gene family and bcl-2 gene family in the rat brain following permanent occlusion of the middle cerebral artery, J. Cereb. Blood Flow Metab., 17, 11, 10.1097/00004647-199701000-00003 · DOI
  5. Bartholdi, 1997, Expression of pro-inflammatory cytokine and chemokine mRNA upon experimental spinal cord injury in mouse: An in situ hybridization study, Eur. J. Neurosci., 9, 1422, 10.1111/j.1460-9568.1997.tb01497.x · DOI
  6. Basso, 1995, A sensitive and reliable locomotor rating scale for open field testing in rats, J. Neurotrauma, 12, 1, 10.1089/neu.1995.12.1 · DOI · Paper page
  7. Bethea, 1998, Traumatic spinal cord injury induces nuclear factor-kappaB activation, J. Neurosci., 18, 3251, 10.1523/JNEUROSCI.18-09-03251.1998 · DOI
  8. Blaschke, 1998, Programmed cell death is a universal feature of embryonic and postnatal neuroproliferative regions throughout the central nervous system, J. Comp. Neurol., 396, 39, 10.1002/(SICI)1096-9861(19980622)396:1<39::AID-CNE4>3.0.CO;2-J · DOI
  9. Brockhaus, 1998, U937 apoptotic cell death by nitric oxide: Bcl-2 downregulation and caspase activation, Exp. Cell Res., 238, 33, 10.1006/excr.1997.3778 · DOI
  10. Cookson, 1998, Peroxynitrite and hydrogen peroxide induced cell death in the NSC34 neuroblastoma × spinal cord cell line: Role of poly (ADP-ribose) polymerase, J. Neurochem., 70, 501, 10.1046/j.1471-4159.1998.70020501.x · DOI
  11. Crowe, 1997, Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys, Nature Med., 3, 73, 10.1038/nm0197-73 · DOI · Paper page
  12. Devereux, 1984, A comprehensive set of sequence analysis programs for the VAX, Nucleic Acids Res., 12, 387, 10.1093/nar/12.1Part1.387 · DOI
  13. Dusart, 1994, Secondary cell death and the inflammatory reaction after dorsal hemisection of the rat spinal cord, Eur. J. Neurosci., 6, 712, 10.1111/j.1460-9568.1994.tb00983.x · DOI
  14. Edwards, 1994, Characterization of apoptosis in cultured rat sympathetic neurons after nerve growth factor withdrawal, J. Cell Biol., 124, 537, 10.1083/jcb.124.4.537 · DOI
  15. Eldadah, 1997, The role of CED-3-related cysteine proteases in apoptosis of cerebellar granule cells, J. Neurosci., 17, 6105, 10.1523/JNEUROSCI.17-16-06105.1997 · DOI
  16. Emery, 1998, Apoptosis after traumatic human spinal cord injury, J. Neurosurg., 89, 911, 10.3171/jns.1998.89.6.0911 · DOI
  17. Fernandes-Alnemri, 1996, In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two fadd like domains, Proc. Natl. Acad. Sci. USA, 93, 7464, 10.1073/pnas.93.15.7464 · DOI
  18. Frankowski, 1995, Function and expression of the Bcl-x gene in the developing and adult nervous system, NeuroReport, 6, 1917, 10.1097/00001756-199510020-00023 · DOI
  19. Gehrmann, 1995, Microglial turnover in the injured CNS: Activated microglia undergo delayed DNA fragmentation following peripheral nerve injury, J. Neuropathol. Exp. Neurol., 54, 680, 10.1097/00005072-199509000-00010 · DOI
  20. Gorman, 1998, Apoptosis in neuronal cells: Role of caspases, NeuroReport, 9, R49, 10.1097/00001756-199807130-00001 · DOI
  21. Gruner, 1991, Assessment of functional recovery after spinal cord injury in rats by reticulospinal-mediated motor evoked responses, Electroencephalogr. Clin. Neurophysiol. Suppl., 43, 297
  22. Hayashi, 1998, Apoptosis of motor neurons with induction of caspases in the spinal cord after ischemia, Stroke, 29, 1007, 10.1161/01.STR.29.5.1007 · DOI
  23. Hirata, 1998, Caspases are activated in a branched protease cascade and control distinct downstream processes in Fas-induced apoptosis, J. Exp. Med., 187, 587, 10.1084/jem.187.4.587 · DOI
  24. Juan, 1996, Molecular characterization of mouse and rat CPP32 beta gene encoding a cysteine protease resembling interleukin-1 beta converting enzyme and CED-3, Oncogene, 13, 749
  25. Katai, 1999, Apoptotic retinal neuronal death by ischemia–reperfusion is executed by two distinct caspase family proteases, Invest. Ophthalmol. Vis. Sci., 40, 2697
  26. Katoh, 1996, Induction and its spread of apoptosis in rat spinal cord after mechanical trauma, Neurosci. Lett., 216, 9, 10.1016/0304-3940(96)12999-2 · DOI
  27. Keane, 1997, Activation of cpp32 during apoptosis of neurons and astrocytes, J. Neurosci. Res., 48, 168, 10.1002/(SICI)1097-4547(19970415)48:2<168::AID-JNR9>3.0.CO;2-A · DOI
  28. Khan, 1983, Acute spinal cord injury in the rat: Comparison of three experimental techniques, Can. J. Neurol. Sci., 10, 161, 10.1017/S031716710004484X · DOI
  29. Klusman, 1997, Effects of pro-inflammatory cytokines in experimental spinal cord injury, Brain Res., 762, 173, 10.1016/S0006-8993(97)00381-8 · DOI
  30. Knerlich, 1999, Temporal profile of expression and cellular localization of inducible nitric oxide synthase, interleukin-1beta and interleukin converting enzyme after cryogenic lesion of the rat parietal cortex, Brain Res. Mol. Brain Res., 68, 73, 10.1016/S0169-328X(99)00064-9 · DOI
  31. Kuida, 1996, Decreased apoptosis in the brain and premature lethality in cpp32 deficient mice, Nature, 384, 368, 10.1038/384368a0 · DOI
  32. Lawson, 1998, The role of apoptosis and excitotoxicity in the death of spinal motoneurons and interneurons after neonatal nerve injury, Neuroscience, 87, 337, 10.1016/S0306-4522(98)00120-1 · DOI
  33. Li, 1996, Apoptosis and expression of bcl 2 after compression trauma to rat spinal cord, J. Neuropathol. Exp. Neurol., 55, 280, 10.1097/00005072-199603000-00003 · DOI
  34. Li, 1997, Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade, Cell, 91, 479, 10.1016/S0092-8674(00)80434-1 · DOI · Paper page
  35. Liang, 1993, Distribution and cloning of eukaryotic mRNAs by means of differential display: Refinements and optimization, Nucleic Acids Res., 21, 3269, 10.1093/nar/21.14.3269 · DOI
  36. Liang, 1992, Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction, Science, 257, 967, 10.1126/science.1354393 · DOI
  37. Liu, 1999, Activation of the apoptotic endonuclease DFF40 (caspase-activated DNase or nuclease): Oligomerization and direct interaction with histone H1, J. Biol. Chem., 274, 13836, 10.1074/jbc.274.20.13836 · DOI
  38. Liu, 1997, Neuronal and glial apoptosis after traumatic spinal cord injury, J. Neurosci., 17, 5395, 10.1523/JNEUROSCI.17-14-05395.1997 · DOI · Paper page
  39. Lunkes, 1998, A cellular model that recapitulates major pathogenic steps of Huntington's disease, Hum. Mol. Genet., 7, 1355, 10.1093/hmg/7.9.1355 · DOI
  40. Martin, 1995, Proteolysis of fodrin (non-erythroid spectrin) during apoptosis, J. Biol. Chem., 270, 6425, 10.1074/jbc.270.12.6425 · DOI
  41. Mattson, 1998, Evidence for synaptic apoptosis, Exp. Neurol., 153, 35, 10.1006/exnr.1998.6863 · DOI
  42. Miura, 1993, Induction of apoptosis in fibroblasts by IL-1 beta-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3, Cell, 75, 653, 10.1016/0092-8674(93)90486-A · DOI
  43. Mukasa, 1997, Specific expression of cpp32 in sensory neurons of mouse embryos and activation of cpp32 in the apoptosis induced by a withdrawal of ngf, Biochem. Biophys. Res. Commun., 231, 770, 10.1006/bbrc.1996.6002 · DOI
  44. Namura, 1998, Activation and cleavage of caspase-3 in apoptosis induced by experimental cerebral ischemia, J. Neurosci., 18, 3659, 10.1523/JNEUROSCI.18-10-03659.1998 · DOI
  45. Nicholson, 1995, Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis, Nature, 376, 37, 10.1038/376037a0 · DOI
  46. Niclou, 1994, Expression of the thrombin receptor mRNA in rat brain, Cell. Mol. Biol., 40, 421
  47. Popovich, 1997, Cellular inflammatory response after spinal cord injury in Sprague–Dawley and Lewis rats, J. Comp. Neurol., 377, 443, 10.1002/(SICI)1096-9861(19970120)377:3<443::AID-CNE10>3.0.CO;2-S · DOI
  48. Ray, 1992, Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme, Cell, 69, 597, 10.1016/0092-8674(92)90223-Y · DOI
  49. Rickers, 1998, Inhibition of CPP32 blocks surface IgM-mediated apoptosis and D4-GDI cleavage in human BL60 Burkitt lymphoma cells, Eur. J. Immunol., 28, 296, 10.1002/(SICI)1521-4141(199801)28:01<296::AID-IMMU296>3.0.CO;2-4 · DOI
  50. Sabol, 1998, Inhibition of apoptosis-associated DNA fragmentation activity in nonapoptotic cells: The role of DNA fragmentation factor-45 (DFF45/ICAD), Biochem. Biophys. Res. Commun., 253, 151, 10.1006/bbrc.1998.9770 · DOI
  51. Siman, 1999, Immunolocalization of caspase proteolysis in situ: Evidence for widespread caspase-mediated apoptosis of neurons and glia in the postnatal rat brain, Neuroscience, 92, 1425, 10.1016/S0306-4522(99)00034-2 · DOI
  52. Smirnova, 1998, Thrombin is a death signal that activates intracellular death protease pathways in motor neurons, J. Neurobiol., 36, 64, 10.1002/(SICI)1097-4695(199807)36:1<64::AID-NEU6>3.0.CO;2-8 · DOI
  53. Soifer, 1994, Disparate temporal expression of the prothrombin and thrombin receptor genes during mouse development, Am. J. Pathol., 144, 60
  54. Springer, 1999, Activation of the caspase-3 apoptotic cascade in traumatic spinal cord injury, Nature Med., 5, 943, 10.1038/11387 · DOI · Paper page
  55. Tewari, 1995, Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase, Cell, 81, 801, 10.1016/0092-8674(95)90541-3 · DOI
  56. Van de Craen, 1997, Characterization of seven murine caspase family members, FEBS Lett., 403, 61, 10.1016/S0014-5793(97)00026-4 · DOI
  57. Wang, 1996, Cleavage of sterol regulatory element binding proteins (SREBPs) by CPP32 during apoptosis, EMBO J., 15, 1012, 10.1002/j.1460-2075.1996.tb00438.x · DOI
  58. Warner, 1998, Genetic regulation of preimplantation mouse embryo survival, J. Exp. Zool., 282, 272, 10.1002/(SICI)1097-010X(199809/10)282:1/2<272::AID-JEZ29>3.0.CO;2-U · DOI
  59. Wolf, 1996, NeuN: A useful neuronal marker for diagnostic histopathology, J. Histochem. Cytochem., 44, 1167, 10.1177/44.10.8813082 · DOI
  60. Yakovlev, 1997, Activation of CPP32-like caspases contributes to neuronal apoptosis and neurological dysfunction after traumatic brain injury, J. Neurosci., 17, 7415, 10.1523/JNEUROSCI.17-19-07415.1997 · DOI
  61. Yamada, 1996, Angiotensin II type 2 receptor mediates programmed cell death, Proc. Natl. Acad. Sci. USA, 93, 156, 10.1073/pnas.93.1.156 · DOI
  62. Yang, 1998, Granzyme B mimics apical caspases: Description of a unified pathway for trans-activation of executioner caspase-3 and -7, J. Biol. Chem., 273, 34278, 10.1074/jbc.273.51.34278 · DOI
  63. Yong, 1998, Apoptosis in cellular compartments of rat spinal cord after severe contusion injury, J. Neurotrauma, 15, 459, 10.1089/neu.1998.15.459 · DOI
  64. Young, 1982, Effect of high-dose corticosteroid therapy on blood flow, evoked potentials, and extracellular calcium in experimental spinal injury, J. Neurosurg., 57, 667, 10.3171/jns.1982.57.5.0667 · DOI
  65. Yuan, 1993, The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme, Cell, 75, 641, 10.1016/0092-8674(93)90485-9 · DOI
  66. Zhou, 1997, Target protease specificity of the viral serpin crma: Analysis of five caspases, J. Biol. Chem., 272, 7797, 10.1074/jbc.272.12.7797 · DOI

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Metadata

Authors
Citron, B. A., Arnold, P. M., Sebastian, C., Qin, F., Malladi, S., Ameenuddin, S., Landis, M. E., & Festoff, B. W.
Venue
Experimental Neurology
Publisher
Elsevier BV
Published
2000-12
Volume
166
Issue
2
Pages
213-226
ISSN
0014-4886
DOI
10.1006/exnr.2000.7523
Cited by
126
References
0
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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CoChat. (2026). Citation check: Rapid Upregulation of Caspase-3 in Rat Spinal Cord after Injury: mRNA, Protein, and Cellular Localization Correlates with Apoptotic Cell Death. https://app.cochat.ai/papers/10.1006/exnr.2000.7523
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Citron, B. A., Arnold, P. M., Sebastian, C., Qin, F., Malladi, S., Ameenuddin, S., Landis, M. E., & Festoff, B. W. (2000). Rapid Upregulation of Caspase-3 in Rat Spinal Cord after Injury: mRNA, Protein, and Cellular Localization Correlates with Apoptotic Cell Death. Experimental Neurology. https://doi.org/10.1006/exnr.2000.7523