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.
authors.affiliation: Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, Texas 77555-1072, USA. Olnesic@utmb.edu
authors.forename: O
authors.initials: O
authors.lastname: Nesic-Taylor
authors.forename: D
authors.initials: D
authors.lastname: Cittelly
authors.forename: Z
authors.initials: Z
authors.lastname: Ye
authors.forename: G Y
authors.initials: GY
authors.lastname: Xu
authors.forename: G
authors.initials: G
authors.lastname: Unabia
authors.forename: J C
authors.initials: JC
authors.lastname: Lee
authors.forename: N M
authors.initials: NM
authors.lastname: Svrakic
authors.forename: X H
authors.initials: XH
authors.lastname: Liu
authors.forename: R J
authors.initials: RJ
authors.lastname: Youle
authors.forename: T G
authors.initials: TG
authors.lastname: Wood
authors.forename: D
authors.initials: D
authors.lastname: McAdoo
authors.forename: K N
authors.initials: KN
authors.lastname: Westlund
authors.forename: C E
authors.initials: CE
authors.lastname: Hulsebosch
authors.forename: J R
authors.initials: JR
authors.lastname: Perez-Polo
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D015514:Oncogene Proteins, Fusion / Q000008:administration & dosage / Q000627:therapeutic use*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D051020:bcl-X Protein
chemical_list: C494813:Bcl2l1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D015514:Oncogene Proteins, Fusion; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D014404:Tubulin; D051020:bcl-X Protein; D010751:Phosphopyruvate Hydratase