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

doi:10.1002/jnr.20400

Exogenous Bcl-X_L 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

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › peer-review

72 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-x_L, Bcl-2, and Bcl-w, using Affymetrix DNA microarrays. Because Bcl-x_L 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-x_L expression. We found Bcl-x_L expressed robustly throughout uninjured spinal cord in both neurons and glia cells. We also found Bcl-x_L localized in different cellular compartments: cytoplasmic, mitochondrial, and nuclear. Bcl-x_L 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-x_L to neuronal death, we augmented endogenous Bcl-x_L levels by administering Bcl-x_L fusion protein (Bcl-x_L FP) into injured spinal cords. Bcl-x_L FP significantly increased neuronal survival, suggesting that SCI-induced changes in Bcl-x_L contribute considerably to neuronal death. Because Bcl-x_L 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 language	English (US)
Pages (from-to)	628-637
Number of pages	10
Journal	Journal of Neuroscience Research
Volume	79
Issue number	5
DOIs	https://doi.org/10.1002/jnr.20400
State	Published - Mar 1 2005

Keywords

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

ASJC Scopus subject areas

Cellular and Molecular Neuroscience

Access to Document

10.1002/jnr.20400

Cite this

@article{cf46da31615e4f93bbe8aad8ee3ff968,

title = "Exogenous Bcl-XL fusion protein spares neurons after spinal cord injury",

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.",

keywords = "Bcl-x, Bcl-x fusion protein, Neurons, Spinal cord injury",

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

year = "2005",

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T1 - Exogenous Bcl-XL fusion protein spares neurons after spinal cord injury

AU - Nesic-Taylor, Olivera

AU - Cittelly, D.

AU - Ye, Z.

AU - Xu, G. Y.

AU - Unabia, G.

AU - Lee, J. C.

AU - Svrakic, N. M.

AU - Liu, X. H.

AU - Youle, R. J.

AU - Wood, T. G.

AU - McAdoo, D.

AU - Westlund, K. N.

AU - Hulsebosch, C. E.

AU - Perez-Polo, J. R.

PY - 2005/3/1

Y1 - 2005/3/1

N2 - 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.

AB - 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.

KW - Bcl-x

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KW - Spinal cord injury

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