Publications (3)12.5 Total impact
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Article: Cdc2-mediated Schwann cell migration during peripheral nerve regeneration.
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ABSTRACT: Schwann cell migration facilitates peripheral nerve regeneration after injury. We have recently found increased activation of Cdc2 kinase in regenerating sciatic nerves. Here we show that Cdc2 phosphorylation of caldesmon regulates Schwann cell migration and nerve regeneration. A robust but transient increase in Cdc2 expression was found in cultured Schwann cells prepared from the sciatic nerve in rats that had undergone crush injury for 7 days. These ;injury-preconditioned' Schwann cells exhibited enhanced migration compared with non-preconditioned control cells and treatment with the cdk inhibitor roscovitine prevented cell migration. After transduction with recombinant Cdc2 DNA adenoviral vectors, Schwann cells were implanted into sciatic nerves; those expressing wild-type Cdc2 migrated further in the distal direction than those expressing dominant-negative Cdc2. We identified caldesmon as a downstream substrate of Cdc2 in Schwann cells and its phosphorylation by Cdc2 changed its subcellular localization. Overexpression of dominant-negative caldesmon significantly counteracted the migration effect caused by Cdc2. Finally, neurite outgrowth of cultured DRG sensory neurons, facilitated by co-culture with injury-preconditioned Schwann cells, was suppressed by roscovitine treatment. The results indicate that activation of the Cdc2-caldesmon pathway is necessary for Schwann cell migration and suggest a role for this pathway in peripheral axonal growth.Journal of Cell Science 02/2007; 120(Pt 2):246-55. · 6.11 Impact Factor -
Article: Involvement of Cdc2 in axonal regeneration enhanced by exercise training in rats.
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ABSTRACT: Physical activity can improve sensorimotor recovery after peripheral nerve injury. We examined the effects of treadmill training (TMT) on axonal regeneration in the injured sciatic nerve of the rat and further investigated cellular and molecular events that underlie enhanced axonal regrowth by training. After crush injury of the sciatic nerves, rats were randomly assigned into either TMT or sedentary groups. Three to 14 d after injury, changes in protein levels in the regenerating nerve were analyzed by Western blotting and immunofluorescence staining. Axonal regeneration was assessed by anterograde and retrograde tracing techniques. The animals' functional recovery was determined by the sciatic functional index. We identified enhanced axonal regrowth in the distal stump of the sciatic nerve 7-14 d after injury in the rats with TMT. Cell division cycle 2 (Cdc2) mRNA and protein levels were highly increased in the injured sciatic nerves 3 and 7 d after injury, and decreased to basal levels 14 d later. Daily TMT accelerated distal shift of Cdc2 mRNA and protein induced in the regenerating nerves, and Cdc2 kinase activity was similarly increased in the distal stump by TMT. Cdc2 protein induced by TMT was mainly colocalized with Schwann cell marker S100beta protein, and correlated with axial distribution pattern of bromodeoxyuridine-labeled proliferating cell population in the regenerating nerve. We further demonstrate that axonal regeneration and motor function recovery after injury, both of which were promoted by TMT, were greatly suppressed by in vivo administration of Cdc2 inhibitor roscovitine. The present data suggest that Cdc2 kinase activated in the regenerating sciatic nerve may play an important role in TMT-mediated enhancement of axonal regeneration.Medicine & Science in Sports & Exercise 08/2006; 38(7):1267-76. · 4.43 Impact Factor -
Article: Growth-promoting activity of Hominis Placenta extract on regenerating sciatic nerve.
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ABSTRACT: Extract of Hominis Placenta (HP) has been used in oriental medicine as an agent for improving physiological function. The present study was conducted to investigate whether HP treatment in an experimental sciatic nerve injury animal model produces growth-promoting effects on regenerating peripheral nerve fibers after injury. After HP was injected into a sciatic nerve injury site, changes in protein levels were analyzed in the regenerating nerve area by Western blotting and immunofluorescence staining analyses. For quantitative assessment of axonal regeneration, a retrograde tracing technique was used to identify the neuronal cell bodies corresponding to regenerating axons, and the extent of neurite outgrowth in cultured dorsal root ganglia (DRG) sensory neurons prepared from animals that had experienced a sciatic nerve crush injury 7 d before neuron collection was analyzed. Induction levels of axonal growth-associated protein (GAP-43) in the injured sciatic nerves were elevated by HP treatment. HP treatment also upregulated cell division cycle 2 (Cdc2) protein levels in the distal stump of the injured sciatic nerve. Induced Cdc2 protein was detected in Schwann cells, suggesting that Cdc2 kinase activity may be involved in the growth-promoting activity of regenerating axons via Schwann cell proliferation. Cell body measurement by retrograde tracing indicated that HP treatment produced significant increases in regenerating motor axons. Finally, HP treatment of cultured DRG sensory neurons significantly increased neurite arborization and elongation. HP promotes the regeneration of injured sciatic axons by upregulating the synthesis of regeneration-related protein factors such as GAP-43 and Cdc2.Acta Pharmacologica Sinica 02/2006; 27(1):50-8. · 1.95 Impact Factor
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Institutions
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2006–2007
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Daejeon University
Taiden, Daejeon, South Korea
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