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ABSTRACT: Mesenchymal stem cells (MSCs) are effective vectors to deliver a gene of interest into degenerating brain. In ex vivo gene therapy, viability of transplanted MSCs are correlated with extent of functional recovery. It has been reported that BDNF facilitates survival of MSCs but dividing MSCs do not express the BDNF receptor, TrkB. In this study, we found that the expression of TrkB is upregulated in human MSCs by addition of forskolin (Fsk), an activator of adenylyl cyclase. To increase survival rate of MSCs and their secretion of tropic factors that enhance regeneration of endogenous cells, we pre-exposed hMSCs with Fsk and transduced with BDNF-adenovirus before the transplantation into the brain of memory deficient rats, a degenerating brain disease model induced by ibotenic acid injection. Viability of MSCs and expression of a GABA synthesizing enzyme were increased. The pre-treatments improved learning and memory detected by the behavioral tests including Y-maze task and passive avoidance test. These results suggest that TrkB expression of hMSCs elevates the neuronal regeneration and efficiency of BDNF delivery for treating degenerative neurological diseases accompanying memory loss.
Biochemical and Biophysical Research Communications 01/2013; · 2.48 Impact Factor
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ABSTRACT: Berberine, an isoquinoline alkaloid component of Coptidis Rhizoma (goldenthread) extract, has been reported to have therapeutic potential for central nervous system disorders such as Alzheimer's disease, cerebral ischemia, and schizophrenia. We have previously shown that berberine promotes the survival and differentiation of hippocampal precursor cells. In a memory-impaired rat model induced by ibotenic acid injection, the survival of pyramidal and granular cells was greatly increased in the hippocampus by berberine administration. In the present study, we investigated the effects of berberine on neurite outgrowth in the SH-SY5Y neuronal cell line and axonal regeneration in the rat peripheral nervous system (PNS). Berberine enhanced neurite extension in differentiating SH-SY5Y cells at concentrations of 0.25-3 μg/mL. In an injury model of the rat sciatic nerve, we examined the neuroregenerative effects of berberine on axonal remyelination by using immunohistochemical analysis. Four weeks after berberine administration (20 mg/kg i.p. once per day for 1 week), the thickness of remyelinated axons improved approximately 1.4-fold in the distal stump of the injury site. Taken together, these results indicate that berberine promotes neurite extension and axonal regeneration in injured nerves of the PNS.
Journal of medicinal food 02/2012; 15(4):413-7. · 1.39 Impact Factor
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ABSTRACT: Deregulation of the expression of human papillomavirus (HPV) oncogenes E6 and E7 plays a pivotal role in cervical carcinogenesis because the E6 and E7 proteins neutralize p53 and Rb tumor suppressor pathways, respectively. In approximately 90% of all cervical carcinomas, HPVs are found to be integrated into the host genome. Following integration, the core-enhancer element and P105 promoter that control expression of E6 and E7 adopt a chromatin structure that is different from that of episomal HPV, and this has been proposed to contribute to activation of E6 and E7 expression. However, the molecular basis underlying this chromatin structural change remains unknown. Previously, BAF53 has been shown to be essential for the integrity of higher-order chromatin structure and interchromosomal interactions. Here, we examined whether BAF53 is required for activated expression of E6 and E7 genes. We found that BAF53 knockdown led to suppression of expression of E6 and E7 genes from HPV integrants in cervical carcinoma cell lines HeLa and SiHa. Conversely, expression of transiently transfected HPV18-LCR-Luciferase was not suppressed by BAF53 knockdown. The level of the active histone marks H3K9Ac and H4K12Ac on the P105 promoter of integrated HPV 18 was decreased in BAF53 knockdown cells. BAF53 knockdown restored the p53-dependent signaling pathway in HeLa and SiHa cells. These results suggest that activated expression of the E6 and E7 genes of integrated HPV is dependent on BAF53-dependent higher-order chromatin structure or nuclear motor activity.
Biochemical and Biophysical Research Communications 07/2011; 412(2):328-33. · 2.48 Impact Factor
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ABSTRACT: Various techniques have been investigated to enhance peripheral nerve regeneration including the application of low-intensity electrical stimulation (ES) and the administration of growth factors, especially brain-derived neurotrophic factor (BDNF). The purpose of this study was to investigate the effects of combining short-term (ES) and recombinant adenoviral vector-mediated BDNF (BDNF-Ad) transfer, in comparison to each sole modality, on peripheral nerve regeneration in a rat model with crush-injured sciatic nerve.
Sixty male Sprague-Dawley rats (250-300 g) were equally distributed into four groups; the control group, the ES group, the BDNF-Ad group, and the combination group (n = 15 each). A standard crush injury was introduced to the sciatic nerve. The control group received no treatment after injury, the ES group received 30 minutes of low-intensity ES, the BDNF-Ad group received an injection of recombinant BDNF-Ad (concentration = 10(11) pfu/μl, 3 μl/rat) after injury, and the combination group received both ES and BDNF-Ad. The rats were followed-up for 3 weeks.
At the end of the follow-up period, the sciatic function index (ES =-39, BDNF-Ad =-38) and number of the retrogradely labeled sensory neurons were significantly increased in the ES group and the BDNF-Ad group (ES = 326, BDNF-Ad = 264), but not in the combined treatment group, compared to the control group (SFI = -53, retrogradely labeled neurons = 229). Axonal counts were highest in the ES group (7,208 axons), axonal densities in the BDNF group (10,598 axons/mm(2)), and the myelin thickness was greater in both groups as compared to the control group. The combined treatment group showed no signs of superior recovery compared to the other groups.
Both the ES and the BDNF-Ad treatments were effective techniques enhancing the sciatic nerve regeneration following a crush injury in rats. Nevertheless, the combined treatment with ES and BDNF-Ad produces neither a synergistic effect nor an improvement in this injury model.
Acta Neurochirurgica 06/2011; 153(10):2021-9. · 1.52 Impact Factor
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ABSTRACT: Berberine is an isoquinoline alkaloid isolated from goldenthread, Coptidis Rhizoma and shown to have many biological and pharmacological effects. We previously reported that berberine promotes cell survival and differentiation of neural stem cells. To examine whether berberine has survival promoting effect on damaged neuronal cells, we generated a cellular model under oxidative stress and an neonatal animal model of degenerating brain disease by injecting MK-801. MK801, a noncompetitive antagonist of N-methyl-d-aspartate (NMDA) receptors, acts as a neurotoxin in developing rats by inhibiting NMDA receptors and induce neuronal cell death. We found that the survival rate of the SH-SY5Y cells under oxidative stress was increased by 287% and 344%, when treated with 1.5 and 3.0µg/ml berberine, respectively. In the developing rats injected by MK801, we observed that TUNEL positive apoptotic cells were outspread in entire brain. The cell death was decreased more than 3 fold in the brains of the MK-801-induced neurodegenerative animal model when berberine was treated to the model animals. This suggests that berberine promotes activity dependent cell survival mediated by NMDA receptor because berberine is known to activate neurons by blocking K(+) current or lowering the threshold of the action potential. Taken together, berberine has neuroprotective effect on damaged neurons and neurodegenerating brains of neonatal animal model induced by MK-801 administration.
Experimental neurobiology. 12/2010; 19(3):140-5.
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ABSTRACT: Neuregulin 1 (NRG1) and epidermal growth factor receptor (ErbB) signaling pathways control Schwann cells during axonal regeneration in an injured peripheral nervous system. We investigated whether a persistent supply of recombinant NRG1 to the injury site could improve axonal growth and recovery of sensory and motor functions in rats during nerve regeneration. We generated a recombinant adenovirus expressing a secreted form of EGF-like domain from Heregulinβ (sHRGβE-Ad). This virus, sHRGβE-Ad allowed for the secretion of 30-50 ng of small sHRGβE peptides per 10(7-8) virus particle outside cells and was able to phosphorylate ErbB receptors. Transduction of the concentrated sHRGβE-Ad into an axotomy model of sciatic nerve damage caused an effective promotion of nerve regeneration, as shown by histological features of the axons and Schwann cells, as well as increased expression of neurofilaments, GAP43 and S100 in the distal stump of the injury site. This result is consistent with longer axon lengths and thicker calibers observed in the sHRGβE-Ad treated animals. Furthermore, sensory and motor functions were significantly improved in sHRGβE-Ad treated animals when evaluated by a behavioral test. These results suggest a therapeutic potential for sHRGβE-Ad in treatment of peripheral nerve injury.
Molecules and Cells 10/2010; 30(5):477-84. · 2.18 Impact Factor
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ABSTRACT: Wogonin is a flavonoid isolated from Scutellaria baicalensis root, and has multiple pharmacological effects, including anti-inflammatory, anti-oxidant, and anti-cancer effects. It is also neuroprotective in the brain under many stress conditions, but wogonin does not elevate neuronal cell survival. Thus, the mechanisms controlling the neuroprotective effect of wogonin are not clear. Neural precursor cells (NPCs), present in the hippocampus and subventricular zone of adult brains, replace damaged cells. In this study we investigated the biological functions underlying the neuroprotective effect of wogonin on NPCs. We initially examined survival of NPCs but found it was slightly reduced at concentrations higher than 2μg/ml. When we explored differentiation of NPCs into neuronal cells, the number of differentiated cells expressing neurofilaments was increased remarkably (fourfold) in the hippocampal NPCs treated with wogonin. Wogonin maximally elevated the expressions of presynaptic protein, synapsin I and postsynaptic protein (PSD95) at a concentration of 0.7μg/ml. Differentiated cells containing longer neurites were significantly increased in cortical NPCs, primarily cultured from rat E14 embryonic brain. Wogonin also promoted differentiation of NPCs into mature neurons in vivo. When transplanted into the adult rat hippocampus, NPCs differentiated into cells expressing NeuN, the mature neuron marker, by 4weeks after transplantation. These data indicate that wogonin induces differentiation of NPCs both in culture and in vivo, and suggest that facilitation of NPC differentiation is a biological activity by which wogonin protects neurons in damaged brain.
Biochemical and Biophysical Research Communications 09/2010; 402(1):42-7. · 2.48 Impact Factor
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ABSTRACT: Although donepezil, a potent acetylcholinesterase (AChE) inhibitor, has been used to treat Alzheimer's disease (AD) due to its neuroprotective effects, its mode of action to inhibit the growth of cancer cells is poorly understood. In the present study, we investigated the pro-apoptotic activities of donepezil in HL-60 human promyelocytic leukemia cells and the underlying molecular mechanism involved. It was found that donepezil induced the apoptosis of HL-60 and U937 cells in a dose- and time-dependent manner, as evidenced by the formation of DNA fragmentation and the accumulation of positive cells for Annexin V. In addition, the activations of caspase-8, -9, and -3 were significantly increased 36 h after donepezil treatment. Furthermore, the broad caspase inhibitor (z-VAD-fmk) blocked donepezil-induced apoptosis. In addition, donepezil was found to cause the loss of mitochondrial membrane potential (DeltaPsi(m)), to increase the release of cytochrome c to the cytosol, and to alter the expressions of Bcl-2 family proteins. Taken together, these results demonstrate for the first time that donepezil displayed an induction of apoptosis in HL-60 cells via a mitochondria-mediated caspase-dependent pathway.
Biological & Pharmaceutical Bulletin 01/2010; 33(6):1054-9. · 1.66 Impact Factor
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Biological & Pharmaceutical Bulletin - BIOL PHARM BULL. 01/2010; 33(6):1054-1059.
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ABSTRACT: Scutellaria baicalensis Georgi (Labiatae) extracts have been used as traditional Korean medicine, to treat cerebral ischemia in addition to bacterial infection and inflammatory diseases.
The improvement effect on learning and memory by the administration of Scutellaria baicalensis extracts was evaluated and the underlying mechanisms were investigated.
Memory behavior was tested by the passive avoidance test and Y-maze test. We also investigated the cells expressing neuronal markers related to memory processes by immunofluorescence staining analysis in memory deficient animal model (Ibo model) rats and in hippocampal progenitor cells.
We found neuronal cells immunoreactive to choline acetyltransferase (ChAT), a marker for cholinergic neurons were increased in the hippocampus, while cells producing GABA and glutamate were not after 30 mg/kg Scutellaria baicalensis administration. Futhermore, Scutellaria baicalensis extracts enhanced the survival of a hippocampal progenitor cell line, HiB5 and its differentiation to ChAT immunoreactive cells. The increased expression of memory related neurotransmitter, NMDA receptor and a reduction of activated microglia in the hippocampus were also observed in the Ibo model when administrated Scutellaria baicalensis extracts.
These results imply that Scutellaria baicalensis has significant neuroprotective effects in the Ibo model.
Journal of ethnopharmacology 01/2009; 122(1):20-7. · 2.32 Impact Factor
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ABSTRACT: The p62 protein has been identified as a major component of the protein aggregations associated with neurodegenerative disease. Oxidative insult has also been identified as a principal cause of neurodegenerative disease. Thus, in the present study, we investigated the potential role of p62 in oxidative stress-induced cell death in SH-SY5Y human neuroblastoma cells. The results indicated that H(2)O(2) treatment induced p62 expression in SH-SY5Y cells. In addition, p62 showed neuroprotective effects against H(2)O(2)-induced cell death in differentiated SH-SY5Y cells. p62 expression prolonged Akt phosphorylation during the later stages of H(2)O(2)-induced cell death. Furthermore, coexpression of p62 and wild-type PDK1, the upstream kinase of Akt, further increased Akt phosphorylation and cell viability, whereas the expression of kinase-defective PDK1 reversed the cytoprotective effects of p62 under oxidative stress. Overexpression of p62 led to the dissociation of PDK1 from the 14-3-3theta protein, which is thought to be a negative regulator of PDK1 kinase activity. These findings suggest a mechanism that involves the p62-mediated modulation of the interaction between signaling molecules and results in cell survival.
Neuroscience Letters 12/2008; 450(1):45-50. · 2.11 Impact Factor
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ABSTRACT: Neurogenesis persists in the adult mammalian brain and can be a target for modulation for therapeutic purposes. This study investigated the effect of a Polygala tenuifolia root extract on the proliferation of a stem cell population in the rat hippocampus. The root extract of P. tenuifolia (2 mg/kg/day, 14 times intraperitoneal injections) increased the incorporation of bromodeoxyuridine (BrdU) into cells in the hippocampal CA1 region. This activity was enriched in the saponin-containing fraction. The majority of cells labelled with BrdU were immunoreactive to nestin or Tuj1 and the percentages of nestin/BrdU- and Tuj1/BrdU-double positive cells were increased by the P. tenuifolia root extract, suggesting that the P. tenuifolia root extract promotes the proliferation of neural stem cells. In addition, this extract promoted the neurite outgrowth of rat neuronal precursor cells, HiB5. These activities of P. tenuifolia root extract may contribute to the therapeutic benefits of herbal medicines containing P. tenuifolia root for the treatment of patients with insomnia, neurosis and dementia.
Phytotherapy Research 08/2008; 22(10):1324-9. · 2.09 Impact Factor
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Hak-Jae Kim,
Min-Ho Kim,
Bong-Keun Choe,
Jong Woo Kim,
Jin Kyung Park,
Ah-Rang Cho,
Hyunsu Bae,
Dong-Hun Shin,
Sung Vin Yim,
KyuBum Kwack, Yunhee Kim Kwon,
Joo-Ho Chung
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ABSTRACT: PDGFRB is located on chromosome 5q31-q32, a chromosomal region identified by linkage analyses to contain a susceptibility gene for schizophrenia (SCZ). Recent research has focused on the role of the N-methyl-d-aspartate (NMDA) receptor in the pathogenesis of SCZ. D4 dopamine receptor-mediated transactivation of the gene encoding platelet-derived growth factor receptor beta (PDGFRB) has immediate effects on synaptic neurotransmission via calcium-dependent inactivation of NMDA receptors. In this study, we investigate the association between the PDGFRB gene and SCZ in a Korean population. We screened 6 single-nucleotide polymorphisms (SNPs) in the 5'-upstream region of PDGFRB and conducted a case-control study of 381 SCZ patients and 752 controls. The genotype and haplotype frequencies of 3 of the 6 SNPs [SNP1 (g.-1924T>C, rs3756314), SNP3 (g.-1772A>G, rs3756312) and SNP4 (rs3756311, g.-1658G>A)] were significantly associated with SCZ [SNP1, corrected p=0.012 (co-dominant model), 0.002 (Dominant model), and 0.506 (Recessive model); SNP3 and 4, corrected p=0.003, 0.009, and 0.049]. Haplotype analysis also revealed that ht1 (CGG) and ht2 (TAA) were significantly associated with SCZ (ht1, corrected p=0.018, 0.340, and 0.010; ht2, corrected p=0.002, 0.009, and 0.016). Transient transfection in neuronal cells revealed that ht1 had higher luciferase activity than the vector alone. Furthermore, Pdgfrb expression was increased in the frontal cortex and hippocampus in a mouse model of SCZ induced by MK801. We conclude that SNPs of the 5'-upstream region of PDGFRB are associated with SCZ in a Korean population. These are weak positives that require future studies to confirm these results.
Schizophrenia Research 07/2008; 103(1-3):201-8. · 4.75 Impact Factor
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Hak-Jae Kim,
Hae Jeong Park,
Kyung Hee Jung,
Ju Yeon Ban,
Jehyun Ra,
Jong Woo Kim,
Jin Kyung Park,
Bong-Keun Choe,
Sung Vin Yim, Yunhee Kim Kwon,
Joo-Ho Chung
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ABSTRACT: To further clarify schizophrenia (SCZ), disrupted in schizophrenia 1 (DISC1) is a promising candidate gene expressed predominantly within the hippocampus. Several lines of evidence suggest that DISC1 may be involved in susceptibility to SCZ. In this study, we investigated whether genetic polymorphisms in the coding region of DISC1 were associated with several SCZ clinical phenotypes in a Korean population. To examine any association between DISC1 and SCZ, we genotyped three clinical single nucleotide polymorphisms (SNPs) (rs3738401, R264Q; rs3738402, L465L; rs821616, S704C) in the coding region of the DISC1 gene using the Illumina Sentrix Array Matrix chip and direct sequencing in 303 patients with SCZ and 300 healthy controls. Our case-control analysis showed that none of these SNPs was associated with SCZ. In further endophenotype stratification, however, we found a significant association between rs821616 and the poor concentration subgroup of SCZ, determined using the Operational Criteria Checklist (codominant model, p=0.015). Our results suggest that DISC1 may be a susceptibility gene for poor concentration among Korean patients with SCZ.
Neuroscience Letters 02/2008; 430(1):60-3. · 2.11 Impact Factor
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ABSTRACT: For many years, it has been demonstrated that neurotrophins regulate the adult nervous system, implicating their potential as therapeutic agents for the treatment of neurodegenerative diseases. We generated adenoviral vectors encoding brain-derived neutotrophin factor (BDNF) and neurotrophin-3 (NT3) and tested either separately or together for the ability to induce differentiation of neuronal precursor cells with two different origins. Separate transduction of adenovirus delivering BDNF (BDNF-Ad) or NT3 (NT3-Ad) induced the neuronal differentiation in hippocampal and cortical precursor cells. NT3-Ad infected cells extended short neurites, whereas BDNFAd infected cells had longer neurites. In the early differentiation of hippocampal precursor cells, simultaneous infection of BDNFAd and NT3-Ad promoted further differentiation and neurite elongation compared with the separate infection of each virus. In contrast, simultaneous infection did not show the synergistic effect in the cortical precursor cells, suggesting that the neurotrophins play distinct roles in different regions of the brain. However, the numbers of neurites and spines per differentiated cells were markedly increased in cortical as well as hippocampal precursor cells, indicating the promotion of efficient neurite elongation and formation of dendritic spine, when BDNF-Ad and NT3-Ad were co-infected. These results suggest more studies in the effect of a combinatorial use of neurotrophins on different sites of brain need to be carried out to develop gene therapy protocols for neurodegenerative diseases.
Journal of Microbiology and Biotechnology 01/2008; 17(12):2033-41. · 1.38 Impact Factor
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ABSTRACT: The conversion of mitotic chromosome into interphase chromatin consists of at least two separate processes, the decondensation of the mitotic chromosome and the formation of the higher-order structure of interphase chromatin. Previously, we showed that depletion of BAF53 led to the expansion of chromosome territories and decompaction of the chromatin, suggesting that BAF53 plays an essential role in the formation of higher-order chromatin structure. We report here that BAF53 is associated with mitotic chromosomes during mitosis. Immunostaining with two different anti-BAF53 antibodies gave strong signals around the DNA of mitotic preparations of NIH3T3 cells and mouse embryo fibroblasts (MEFs). The immunofluorescent signals were located on the surface of mitotic chromosomes prepared by metaphase spread. BAF53 was also found in the mitotic chromosome fraction of sucrose gradients. Association of BAF53 with mitotic chromosomes would allow its rapid activation on the chromatin upon exit from mitosis.
Molecules and Cells 11/2007; 24(2):288-93. · 2.18 Impact Factor
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ABSTRACT: Chromosomes are compartmentalized into discrete chromosome territories during interphase in mammalian cells. A chromosome territory is generated by the tendency of chromatin to occupy the smallest shell volume, which is determined by the polymeric properties and interactions of the internal meshwork of the chromatin fiber. Here, we show that BAF53 knockdown by small interfering RNA interference led to the expansion of chromosome territories. This was accompanied by a reduction in chromatin compaction, an increase in the micrococcal nuclease sensitivity of the chromatin, and an alteration in H3-K9 and H3-K79 dimethylation. Interestingly, the BAF53 knockdown cells suffer a cell cycle defect. Despite the significant irregularity and decompaction of the polynucleosomes isolated from the BAF53 knockdown cells, the chromatin loading of H1 and core histones remained unaltered, as did the nucleosome spacing. The histone hyperacetylation and down-regulation of BRG-1, mBrm, and Tip49, the catalytic components of the SWI/SNF complex and the TIP60 complex, respectively, did not expand chromosome territories. These results indicate that BAF53 contributes to the polymeric properties and/or the internal meshwork interactions of the chromatin fiber probably via a novel mechanism.
Molecular Biology of the Cell 11/2007; 18(10):4013-23. · 4.94 Impact Factor
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ABSTRACT: Amyloid precursor protein generates the secreted amyloid precursor protein alpha, which protects hippocampal neurons from ischemic injury and facilitates neuronal survival and synaptogenesis in the developing nervous system. Here, we examined whether platelet-derived growth factor regulates the generation of secreted amyloid precursor protein alpha during the neuronal differentiation of hippocampal precursor cells, HiB5. We showed that platelet-derived growth factor promoted amyloid precursor protein production and secreted amyloid precursor protein alpha secretion. These effects of platelet-derived growth factor were diminished by the PI3K-specific inhibitor wortmannin and the protein kinase C-specific inhibitor GF109203X, suggesting the involvement of the PI3K and protein kinase C-signaling pathway. Furthermore, the conditioned media enriched with secreted amyloid precursor protein alpha promoted the survival of HiB5 cells during neuronal differentiation. These results suggest that the neurotrophic effect of platelet-derived growth factor is mediated in part via upregulation of the expression and release of secreted amyloid precursor protein alpha.
Neuroreport 09/2007; 18(12):1225-9. · 1.66 Impact Factor
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ABSTRACT: Genetically modified mesenchymal stem cells (MSCs) are potentially valuable tools for the novel treatment of human illnesses. Here, we investigated whether gene transfers by self-complementary adeno-associated viruses (scAAV) lead to promising genetic modification in human bone marrow and umbilical cord blood MSCs. Of the various scAAVs, scAAV2, and scAAV5 effectively and safely expressed transgenes in both hMSCs. Transduction efficiency with scAAV2 at 1000 multiplicity of infection was 66.3+/-9.4% and 67.6+/-6.7% in bone marrow and umbilical cord blood MSCs, respectively. A co-infection study showed that the distinct scAAV2 and scAAV5 can effectively express different transgenes in the same hMSC. hMSCs transduced by scAAVs showed long-term gene expression for three months in rat brains. Genetic modification by scAAVs did not affect osteogenic differentiation of hMSCs. Therefore, the present study strongly supports the promising potential of scAAVs as a technical platform for safe, long-term transgene expression in hMSCs.
Biochemical and Biophysical Research Communications 09/2007; 360(3):573-9. · 2.48 Impact Factor
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ABSTRACT: HiB5 is a multipotent hippocampal stem cell line whose differentiation into cells of a neuronal phenotype is promoted by neurotrophic factors such as PDGF and brain-derived neurotrophic factor (BDNF). We examined the potential role of Src homology 2 (SH2)-containing protein tyrosine phosphatase (Shp2) in this differentiation process. We found that Shp2 became tyrosine phosphorylated following PDGF treatment. Wild-type Shp2 enhanced the expression of neurofilament, synapsin I and PSD95 by PDGF and BDNF, whereas their expression was attenuated by the catalytically inactive mutants Shp2C/S and Shp2DeltaP. Formation of dendritic spine-like structures increased with wild-type Shp2, but diminished with Shp2C/S and Shp2DeltaP. PSD95, localized in the post-synaptic density region of dendritic spines, PDGFRbeta and TrkB were co-immunoprecipitated with Shp2 antibodies. These results suggest that Shp2 plays a positive role in mediating PDGF- and BDNF-activated signaling which promotes the formation of dendritic spines.
Archives of Pharmacal Research 07/2007; 30(6):750-4. · 1.59 Impact Factor
