title: Systemic administration of PEP-1-SOD1 fusion protein improves functional recovery by inhibition of neuronal cell death after spinal cord injury.
abstract: 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.
authors: Age-Related and Brain Diseases Research Center, Kyung Hee University, Seoul 130-701, Korea. tyune@khu.ac.kr
authors: Tae Young
authors: TY
authors: Yune
authors: Jee Youn
authors: JY
authors: Lee
authors: Mei Hua
authors: MH
authors: Jiang
authors: Dae Won
authors: DW
authors: Kim
authors: Soo Young
authors: SY
authors: Choi
authors: Tae Hwan
authors: TH
authors: Oh
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D003543:Cysteamine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D013482:Superoxide Dismutase / Q000008:administration & dosage*; D000072105:Superoxide Dismutase-1
chemical_list: D000975:Antioxidants; C503924:Pep-1 peptide; D010455:Peptides; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; C000606290:SOD1 protein, human; D003543:Cysteamine; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1