Phosphorylation of Bcl-xL after spinal cord injury
Brain and Mind Institute
Spinal cord injury (SCI)-induced functional impairment results from secondary apoptosis regulated in part by SCI-induced decreases in the antiapoptotic protein Bcl-x(L). We assessed the role that Bcl-x(L) subcellular rerouting and posttranslational phosphorylation play in Bcl-x(L) decreases in a contusion model of rat SCI. Immunohistochemical analysis showed the presence of Bcl-x(L) in neurons and oligodendrocytes, but not in astrocytes and microglia, whereas phosphorylated Bcl-x(L) (P-ser(62)-Bcl-x(L)) was present only in neurons. Western blot analyses showed Bcl-x(L) present in mitochondria, endoplasmic reticulum, nuclei, and cytosolic extracts, whereas P-ser(62)-Bcl-x(L) was restricted to organelles. During the first 24 hr after SCI, Bcl-x(L) 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-ser(62)-Bcl-x(L) levels in organelles. However, P-ser(62)-Bcl-x(L), 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-x(L) and neuronal apoptosis, supporting the hypothesis that Bcl-x(L) phosphorylation is proapoptotic. Activated microglia/macrophages robustly expressed Bcl-x(L) 7 days after SCI, and a subpopulation showing nuclear condensation also expressed P-ser(62)-Bcl-x(L). Therefore, phosphorylation of Bcl-x(L) may have opposite effects in injured spinal cords: 1) it may decrease levels of the antiapoptotic Bcl-x(L) in neurons contributing to neuronal death, and 2) it may promote apoptosis in activated microglia/macrophages, thus curtailing the inflammatory cascades associated with SCI.
Journal of Neuroscience Research
Cittelly, D. M.,
Taylor,, O. N.,
Perez-Polo, J. R.
(2007). Phosphorylation of Bcl-xL after spinal cord injury. Journal of Neuroscience Research, 85(9), 1894-1911.
Available at: https://ecommons.aku.edu/bmi/45