Exogenous Bcl-XL fusion protein spares neurons after spinal cord injury

Olivera Nesic-Taylor, D. Cittelly, Z. Ye, G. Y. Xu, G. Unabia, J. C. Lee, N. M. Svrakic, X. H. Liu, R. J. Youle, T. G. Wood, D. McAdoo, K. N. Westlund, C. E. Hulsebosch, J. R. Perez-Polo

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

Spinal cord injury (SCI) induces neuronal death, including apoptosis, which is completed within 24 hr at and around the impact site. We identified early proapoptotic transcriptional changes, including upregulation of proapoptotic Bax and downregulation of antiapoptotic Bcl-xL, Bcl-2, and Bcl-w, using Affymetrix DNA microarrays. Because Bcl-xL is the most robustly expressed antiapoptotic Bcl-2 molecule in adult central nervous system, we decided to characterize better the effect of SCI on Bcl-xL expression. We found Bcl-xL expressed robustly throughout uninjured spinal cord in both neurons and glia cells. We also found Bcl-xL localized in different cellular compartments: cytoplasmic, mitochondrial, and nuclear. Bcl-xL protein levels decreased in the cytoplasm and mitochondria 2 hr after SCI and persisted for 24 hr. To test the contribution of proapoptotic decreases in Bcl-xL to neuronal death, we augmented endogenous Bcl-xL levels by administering Bcl-xL fusion protein (Bcl-xL FP) into injured spinal cords. Bcl-xL FP significantly increased neuronal survival, suggesting that SCI-induced changes in Bcl-xL contribute considerably to neuronal death. Because Bcl-xL FP increases survival of dorsal horn neurons and ventral horn motoneurons, it could become clinically relevant in preserving sensory and motor functions after SCI.

Original languageEnglish (US)
Pages (from-to)628-637
Number of pages10
JournalJournal of Neuroscience Research
Volume79
Issue number5
DOIs
StatePublished - Mar 1 2005

Keywords

  • Bcl-x
  • Bcl-x fusion protein
  • Neurons
  • Spinal cord injury

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Exogenous Bcl-X<sub>L</sub> fusion protein spares neurons after spinal cord injury'. Together they form a unique fingerprint.

  • Cite this

    Nesic-Taylor, O., Cittelly, D., Ye, Z., Xu, G. Y., Unabia, G., Lee, J. C., Svrakic, N. M., Liu, X. H., Youle, R. J., Wood, T. G., McAdoo, D., Westlund, K. N., Hulsebosch, C. E., & Perez-Polo, J. R. (2005). Exogenous Bcl-XL fusion protein spares neurons after spinal cord injury. Journal of Neuroscience Research, 79(5), 628-637. https://doi.org/10.1002/jnr.20400