Phosphorylation of Bcl-xL after spinal cord injury

Diana M. Cittelly, Olivera Nesic-Taylor, J. Regino Perez-Polo

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    14 Scopus citations


    Spinal cord injury (SCI)-induced functional impairment results from secondary apoptosis regulated in part by SCI-induced decreases in the antiapoptotic protein Bcl-xL. We assessed the role that Bcl-x L subcellular rerouting and posttranslational phosphorylation play in Bcl-xL decreases in a contusion model of rat SCI. Immunohistochemical analysis showed the presence of Bcl-xL in neurons and oligodendrocytes, but not in astrocytes and microglia, whereas phosphorylated Bcl-xL (P-ser62-Bcl-xL) was present only in neurons. Western blot analyses showed Bcl-xL present in mitochondria, endoplasmic reticulum, nuclei, and cytosolic extracts, whereas P-ser62-Bcl-xL was restricted to organelles. During the first 24 hr after SCI, Bcl-xL levels decreased in all fractions but with a different time course, suggesting an independent regulation of Bcl-x L shuttling from the cytosol to each compartment after SCI. SCI did not affect P-ser62-Bcl-xL levels in organelles. However, P-ser62-Bcl-xL, which was not detected in the cytosolic fraction of uninjured spinal cord, appeared in the cytosol as early as 15 min postcontusion, suggesting a role for phosphorylation in SCI-induced Bcl-x L-decreases. Using an in vitro model, we observed a correlation between levels of cytosolic phosphorylated Bcl-xL and neuronal apoptosis, supporting the hypothesis that Bcl-xL phosphorylation is proapoptotic. Activated microglia/macrophages robustly expressed Bcl-x L 7 days after SCI, and a subpopulation showing nuclear condensation also expressed P-ser62-Bcl-xL. Therefore, phosphorylation of Bcl-xL may have opposite effects in injured spinal cords: 1) it may decrease levels of the antiapoptotic Bcl-xL in neurons contributing to neuronal death, and 2) it may promote apoptosis in activated microglia/macrophages, thus curtailing the inflammatory cascades associated with SCI.

    Original languageEnglish (US)
    Pages (from-to)1894-1911
    Number of pages18
    JournalJournal of Neuroscience Research
    Issue number9
    StatePublished - Jul 2007


    • Apoptosis
    • Endoplasmic reticulum
    • Injury
    • Mitochondria
    • Neuronal death
    • Phosphorylation

    ASJC Scopus subject areas

    • Cellular and Molecular Neuroscience


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