title: Human umbilical cord blood cells protect oligodendrocytes from brain ischemia through Akt signal transduction.
abstract: Human umbilical cord blood (HUCB) cells protect the brain against ischemic injury, yet the mechanism of protection remains unclear. Using both in vitro and in vivo paradigms, this study examined the role of Akt signaling and peroxiredoxin 4 expression in human umbilical cord blood cell-mediated protection of oligodendrocytes from ischemic conditions. As previously reported, the addition of HUCB cells to oligodendrocyte cultures prior to oxygen glucose deprivation significantly enhanced oligodendrocyte survival. The presence of human umbilical cord blood cells also increased Akt phosphorylation and elevated peroxiredoxin 4 expression in oligodendrocytes. Blocking either Akt or peroxiredoxin 4 activity with Akt Inhibitor IV or a peroxiredoxin 4-neutralizing antibody, respectively, negated the protective effects of human umbilical cord blood cells. In vivo, systemic administration of human umbilical cord blood cells 48 h after middle cerebral artery occlusion increased Akt phosphorylation and peroxiredoxin 4 protein expression while reducing proteolytic cleavage of caspase 3 in oligodendrocytes residing in the ipsilateral external capsule. Moreover, human umbilical cord blood cells protected striatal white matter bundles from degeneration following middle cerebral artery occlusion. These results suggest that the soluble factors released from human umbilical cord blood cells converge on Akt to elevate peroxiredoxin 4 levels, and these effects contribute to oligodendrocyte survival.
authors.affiliation: Department of Molecular Pharmacology and Physiology, School of Basic Biomedical Sciences, College of Medicine, University of South Florida, Tampa, Florida 33612, USA.
authors.forename: Derrick D
authors.initials: DD
authors.lastname: Rowe
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Leonardo
authors.forename: Jesus A
authors.initials: JA
authors.lastname: Recio
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Collier
authors.forename: Alison E
authors.initials: AE
authors.lastname: Willing
authors.forename: Keith R
authors.initials: KR
authors.lastname: Pennypacker
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D053148:Caspase 3 / Q000096:biosynthesis; D002470:Cell Survival; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology; D054464:Peroxiredoxins / Q000096:biosynthesis; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D009419:Nerve Tissue Proteins; D054464:Peroxiredoxins; C515982:Prdx4 protein, rat; D051057:Proto-Oncogene Proteins c-akt; C505410:Casp3 protein, rat; D053148:Caspase 3