Exogenous Bcl-xl fusion protein spares neurons after spinal cord injury
Article first published online: 24 JAN 2005
Copyright © 2005 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 79, Issue 5, pages 628–637, 1 March 2005
How to Cite
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. and Perez-Polo, J.R. (2005), Exogenous Bcl-xl fusion protein spares neurons after spinal cord injury. J. Neurosci. Res., 79: 628–637. doi: 10.1002/jnr.20400
- Issue published online: 16 FEB 2005
- Article first published online: 24 JAN 2005
- Manuscript Accepted: 22 NOV 2004
- Manuscript Received: 6 NOV 2004
- Mission Connect, TIRR Foundation
- spinal cord injury;
- Bcl-xL fusion protein;
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. © 2005 Wiley-Liss, Inc.