TY - JOUR T1 - Fas Receptor and Neuronal Cell Death after Spinal Cord Ischemia JF - The Journal of Neuroscience JO - J. Neurosci. SP - 6879 LP - 6887 DO - 10.1523/JNEUROSCI.20-18-06879.2000 VL - 20 IS - 18 AU - Kohji Matsushita AU - Yongqin Wu AU - Jianhua Qiu AU - Loic Lang-Lazdunski AU - Lorenz Hirt AU - Christian Waeber AU - Bradley T. Hyman AU - Junying Yuan AU - Michael A. Moskowitz Y1 - 2000/09/15 UR - http://www.jneurosci.org/content/20/18/6879.abstract N2 - Cell death from spinal cord injury is mediated in part by apoptotic mechanisms involving downstream caspases (e.g., caspase-3). Upstream mechanisms may involve other caspases such as procaspase-8, a 55 kDa apical caspase, which we found constitutively expressed within spinal cord neurons along with Fas. As early as 1.5 hr after transient ischemia, activated caspase-8 (p18) and caspase-8 mRNA appeared within neurons in intermediate gray matter and in medial ventral horn. We also detected evidence for an increase in death receptor complex by co-immunoprecipitation using Fas and anti-procaspase-8 after ischemia. At early time points, Fas and p18 were co-expressed within individual neurons, as were activated caspase-8 and caspase-3. Moreover, we detected p18 in cells before procaspase-3 cleavage product (p20), suggesting sequential activation. The appearance of cytosolic cytochrome c and gelsolin cleavage after ischemia was consistent with mitochondrial release and caspase-3 activation, respectively. Numerous terminal deoxynucleotidyl transferase-mediated DNA nick end-labeling-positive neurons contained p18 or p20 (65 and 80%, respectively), thereby supporting the idea that cells undergoing cell death contain both processed caspases. Our data are consistent with the idea that transient spinal cord ischemia induces the formation of a death-inducing signaling complex, which may participate in caspase-8 activation and sequential caspase-3 cleavage. Death receptors as well as downstream caspases may be useful therapeutic targets for limiting the death of cells in spinal cord. ER -