کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1910562 | 1046776 | 2008 | 11 صفحه PDF | دانلود رایگان |
Spinal cord injury (SCI) produces excessive levels of reactive oxygen species (ROS) that induce apoptosis of neurons. Cu,Zn-superoxide dismutase (SOD1) is a key antioxidant enzyme that detoxifies intracellular ROS, thereby protecting cells from oxidative damage. PEP-1 is a peptide carrier capable of delivering full-length native peptides or proteins into cells. In the study described here, we fused a human SOD1 gene with PEP-1 in a bacterial expression vector to produce a genetic in-frame PEP-1–SOD1 fusion protein; we then investigated the neuroprotective effect of the fusion protein after SCI. The expressed and purified PEP-1–SOD1 was efficiently delivered into cultured cells and spinal cords in vivo, and the delivered fusion protein was biologically active. Systemic administration of PEP-1–SOD1 significantly decreased levels of ROS and protein carbonylation and nitration in spinal motor neurons after injury. PEP-1–SOD1 treatment also significantly inhibited mitochondrial cytochrome c release and activation of caspase-9 and caspase-3 in spinal cords after injury. Furthermore, PEP-1–SOD1 treatment significantly reduced ROS-induced apoptosis of motor neurons and improved functional recovery after SCI. These results suggest that PEP-1–SOD1 may provide a novel strategy for the therapeutic delivery of antioxidant enzymes that protect neurons from ROS after SCI.
Journal: Free Radical Biology and Medicine - Volume 45, Issue 8, 15 October 2008, Pages 1190–1200