title: PEP-1-frataxin significantly increases cell proliferation and neuroblast differentiation by reducing lipid peroxidation in the mouse dentate gyrus.
abstract: Frataxin plays important roles in the mitochondrial respiratory chain and in the differentiation of neurons during early development. In this study, we observed the effects of frataxin on cell proliferation and neuroblast differentiation in the mouse hippocampal dentate gyrus. For this, we constructed an expression vector, PEP-1, that was fused with frataxin to create a PEP-1-frataxin fusion protein that easily penetrated frataxin into the blood-brain barrier. Three mg/kg PEP-1-frataxin was intraperitoneally administered to mice once a day for 2 weeks. The administration of PEP-1 alone did not result in any significant changes in the number of Ki67-positive cells and doublecortin (DCX)-immunoreactive neuroblasts in the mouse dentate gyrus. However, the administration of PEP-1-frataxin significantly increased the number of Ki67-positive cells and DCX-immunoreactive neuroblasts in the mouse dentate gyrus. In addition, PEP-1-frataxin significantly reduced 4-hydroxynonenal protein levels and malondialdehyde formation, while Cu, Zn-superoxide dismutase protein levels were maintained. These results suggest that frataxin effectively increased cell proliferation and neuroblast differentiation by decreasing lipid peroxidation in the dentate gyrus.
authors: Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 151-742, South Korea.
authors: Woosuk
authors: W
authors: Kim
authors: Dae Won
authors: DW
authors: Kim
authors: Bich Na
authors: BN
authors: Shin
authors: Dae Young
authors: DY
authors: Yoo
authors: Sung Min
authors: SM
authors: Nam
authors: Mi Jin
authors: MJ
authors: Kim
authors: Jung Hoon
authors: JH
authors: Choi
authors: Yeo Sung
authors: YS
authors: Yoon
authors: Moo-Ho
authors: MH
authors: Won
authors: Soo Young
authors: SY
authors: Choi
authors: In Koo
authors: IK
authors: Hwang
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D033862:Iron-Binding Proteins / Q000494:pharmacology*; D019394:Ki-67 Antigen / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D058953:Neural Stem Cells; D055495:Neurogenesis; D009479:Neuropeptides / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D000096923:Frataxin
chemical_list: D000447:Aldehydes; D003543:Cysteamine; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D033862:Iron-Binding Proteins; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D010455:Peptides; D011993:Recombinant Fusion Proteins; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000096923:Frataxin; C000714847:Dcx protein, mouse; C503924:Pep-1 peptide; C000606291:Sod1 protein, mouse; C027576:4-hydroxy-2-nonenal