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991.
Kim W Kim DW Shin BN Yoo DY Nam SM Kim MJ Choi JH Yoon YS Won MH Choi SY Hwang IK 《Neurochemical research》2011,36(12):2452-2458
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. 相似文献
992.
Yoo DY Kim W Nam SM Kim DW Chung JY Choi SY Yoon YS Won MH Hwang IK 《Neurochemical research》2011,36(10):1850-1857
We previously observed that pyridoxine (vitamin B6) significantly increased cell proliferation and neuroblast differentiation without any neuronal damage in the hippocampus.
In this study, we investigated the effects of sodium butyrate, a histone deacetylase (HDAC) inhibitor which serves as an epigenetic
regulator of gene expression, on pyridoxine-induced neural proliferation and neurogenesis induced by the increase of neural
proliferation in the mouse dentate gyrus. Sodium butyrate (300 mg/kg, subcutaneously), pyridoxine (350 mg/kg, intraperitoneally),
or combination with sodium butyrate were administered to 8-week-old mice twice a day and once a day, respectively, for 14 days.
The administration of sodium butyrate significantly increased acetyl-histone H3 levels in the dentate gyrus. Sodium butyrate
alone did not show the significant increase of cell proliferation in the dentate gyrus. But, pyridoxine alone significantly
increased cell proliferation. Sodium butyrate in combination with pyridoxine robustly enhanced cell proliferation and neurogenesis
induced by the increase of neural proliferation in the dentate gyrus, showing that sodium butyrate treatment distinctively
enhanced development of neuroblast dendrites. These results indicate that an inhibition of HDAC synergistically promotes neurogenesis
induced by a pyridoxine and increase of neural proliferation. 相似文献
993.
994.
The aim of this study was to identify the candidate causal single nucleotide polymorphisms (SNPs) and candidate causal mechanisms that contribute to bone mineral density (BMD) and to generate a SNP to gene to pathway hypothesis using an analytical pathway-based approach. We used hip BMD GWAS data of the genotypes of 301,019 SNPs in 5,715 Europeans. ICSNPathway (identify candidate causal SNPs and pathways) analysis was applied to the BMD GWAS dataset. The first stage involved the pre-selection of candidate causal SNPs by linkage disequilibrium analysis and the functional SNP annotation of the most significant SNPs found. The second stage involved the annotation of biological mechanisms for the pre-selected candidate causal SNPs using improved-gene set enrichment analysis. ICSNPathway analysis identified seven candidate SNPs, eight candidate pathways, and seven hypothetical biological mechanisms. Eight pathways are as follows; gamma-hexachlorocyclohexane degradation (nominal p-value < 0.001, false discovery rate (FDR) <0.001), regulation of the smoothened signaling pathway (nominal p-value < 0.001, FDR = 0.016), TACI and BCMA stimulation of B cell immune response (nominal p-value < 0.001, FDR = 0.021), endonuclease activity (nominal p-value = 0.001, FDR = 0,026), regulation of defense response to virus (nominal p-value = 0.001, FDR = 0.028), serine_type_endopeptidase_inhibitor_activity (nominal p-value = 0.001, FDR = 0.044), endoribonuclease activity (nominal p-value = 0.002, FDR = 0.045), and myeloid leukocyte differentiation (nominal p-value = 0.001, FDR = 0.050). The most significant causal pathway was gamma-hexachlorocyclohexane degradation. CYP3A5, PON2, PON3, CMBL, PON1, ALPL, CYP3A43, CYP3A7, ACP6, ACPP, and ALPI (p < 0.05) are involved in the pathway of gamma-hexachlorocyclohexane degradation. Further examination of the gene contents revealed that DBR1, DICER1, EXO1, FEN1, POP1, POP4, RPP30, and RPP38 were involved in 2 of the 8 pathways (p < 0.05). By applying ICSNPathway analysis to BMD GWAS data, we identified seven candidate SNPs and eight pathways involving gamma-hexachlorocyclohexane degradation, which may contribute to low BMD. 相似文献
995.
The aim of this study was to explore whether the cytotoxic T lymphocyte associated antigen-4 (CTLA-4) or tumor necrosis factor-α
(TNF-α) polymorphisms contribute to anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) susceptibility.
The authors conducted a meta-analysis on associations between polymorphisms of the 3′ untranslated region (UTR) microsatellite
at exon 3, exon 4 CT60 (A/G), exon 1 +49 (A/G), and promoter -318 (C/T) of CTLA-4, and TNF-α promoter-308 (A/G) and AAV susceptibility
as determined using; (1) allelic contrast and (2) homozygote contrast, (3) recessive, and (4) dominant models. A total of
11 comparisons were considered in this meta-analysis. These studies encompassed 7 CTLA-4 studies and 4 TNF-α studies in 10
European populations and 1 Asian population. The (AT)n repeat polymorphisms of CTLA-4 were found to be significantly associated with AAV in European populations (OR of 86 vs. xx
allele = 0.402, 95% CI = 0.184–0.875, P = 0.022). The one study conducted on this polymorphism in Asians showed no significant association with AAV. Meta-analysis
of the 86/86 (recessive effect), 86/86 and 86/xx (dominant effect), and 86/86 vs. xx/xx (homozygote contrast) of the (AT)n repeat revealed a significant association with AAV in Europeans. Both the CTLA-4 CT60 and +49 polymorphisms were found to be significantly associated with AAV in European populations, and allele and genotype-based
analyses showed a significant association between the CTLA-4 CT60 and +49 polymorphisms with AAV in Europeans (OR of the A allele of CT60 = 0.769, 95% CI = 0.619–0.017, P = 0.035; OR of the T allele of +49 = 1.382, 95% CI = 1.147–1.664, P = 0.001, respectively). Meta-analysis of the CTLA-4 -318 polymorphism failed to identify any association with AAV. Furthermore, meta-analysis of the AA genotype, the AA and
AG genotypes, and the A allele of TNF-α failed to reveal any association with Wegener’s granulomatosis (WG). This meta-analysis
demonstrates that the CTLA-4 polymorphisms confer susceptibility to AAV in Europeans. In contrast, no association was found
between the TNF-α-308 polymorphism and susceptibility to WG in Europeans. 相似文献
996.
Kim W Kim DW Yoo DY Chung JY Hwang IK Won MH Choi SY Jeon SW Jeong JH Hwang HS Moon SM 《Neurochemical research》2012,37(2):307-313
A rabbit model of spinal cord ischemia has been introduced as a good model to investigate the pathophysiology of ischemia-reperfusion (I-R)-induced paraplegia. In the present study, we observed the effects of Cu,Zn-superoxide dismutase (SOD1) against ischemic damage in the ventral horn of L(5-6) levels in the rabbit spinal cord. For this study, the expression vector PEP-1 was constructed, and this vector was fused with SOD1 to create a PEP-1-SOD1 fusion protein that easily penetrated the blood-brain barrier. Spinal cord ischemia was induced by transient occlusion of the abdominal aorta for 15 min. PEP-1-SOD1 (0.5 mg/kg) was intraperitoneally administered to rabbits 30 min before ischemic surgery. The administration of PEP-1-SOD1 significantly improved neurological scores compared to those in the PEP-1 (vehicle)-treated ischemia group. Also, in this group, the number of cresyl violet-positive cells at 72 h after I-R was much higher than that in the vehicle-treated ischemia group. Malondialdehyde levels were significantly decreased in the ischemic spinal cord of the PEP-1-SOD1-treated ischemia group compared to those in the vehicle-treated ischemia group. In contrast, the administration of PEP-1-SOD1 significantly ameliorated the ischemia-induced reduction of SOD and catalase levels in the ischemic spinal cord. These results suggest that PEP-1-SOD1 protects neurons from spinal ischemic damage by decreasing lipid peroxidation and maintaining SOD and catalase levels in the ischemic rabbit spinal cord. 相似文献
997.
Yoo DY Kim W Kim IH Nam SM Chung JY Choi JH Yoon YS Won MH Hwang IK 《Neurochemical research》2012,37(1):223-231
We previously reported that sodium butyrate (SB), a histone deacetylase inhibitor, robustly increased pyridoxine-induced cell
proliferation and neuroblast differentiation in the dentate gyrus of the adult mouse. In this study, we investigated the effects
of treatment with SB combined with pyridoxine on cell proliferation and neuroblast differentiation in the dentate gyrus of
a mouse model of aging induced by d-galactose (d-gal). d-gal was administered to 20-week-old male mice (d-gal mice) for 10 weeks to induce changes that resemble natural aging in animals. Seven weeks after d-gal (100 mg/kg) treatment, vehicle (physiological saline; d-gal-vehicle mice) and SB (300 mg/kg) combined with pyridoxine (Pyr; 350 mg/kg) were administered to the mice (d-gal-Pyr-SB mice) for 3 weeks. Escape latency under water maze in the d-gal mice was longer than that in the control mice. In the d-gal-Pyr-SB mice, escape latency was similar to that in the control mice. In the d-gal mice, many cells in the granule cell layer of the dentate gyrus showed pyknosis and condensation of the cytoplasm. However,
in the d-gal-Pyr-SB mice, such cellular changes were rarely found. Furthermore, the d-gal mice showed a great reduction in cell proliferation (Ki67-positive cells) and neuroblast differentiation (doublecortin-positive
neuroblasts) in the dentate gyrus compared to control mice. However, in the d-gal-Pyr-SB mice, cell proliferation and neuroblast differentiation were markedly increased in the dentate gyrus. Furthermore,
the administration of pyridoxine with sodium butyrate significantly increased Ser133-phosphorylated cyclic AMP response element
binding protein in the dentate gyrus. These results indicate that the combination treatment of Pyr with SB in d-gal mice ameliorated the d-gal-induced reduction in cell proliferation, neuroblast differentiation, and memory deficits. 相似文献
998.
Hwang IK Ahn JH Yoo DY Lee CH Yoo KY Choi JH Moon SM Shin HC Won MH 《Neurochemical research》2012,37(3):480-486
The activation of caspase-3 is considered to be a reliable marker for apoptotic cell death, and a 120-kDa fragment of αII-spectrin
is generated by caspase-3 mediated cleavage of this structural protein. In the present study, we compared cleaved αII-spectrin
(120-kDa) and cleaved caspase-3-immunoreactive cells and their protein levels in the cervical (C5–C6) and lumbar (L3–L4) levels of the spinal cord in adult (1–2 year-old) and aged (10–12 year-old) dogs (German shepherds). Weak cleaved αII-spectrin
and cleaved caspase-3 immunoreactivity was found in neurons of the adult group; however, their immunoreactivity was distinctively
increased in the neuronal cytoplasm in the aged group compared to those in the adult group, although the distribution pattern
of their neurons was similar between the adult and age group. In addition, cleaved αII-spectrin and cleaved caspase-3 levels
in the aged spinal cord were markedly increased compared to those in the adult group. These findings suggest that the increases
of cleaved αII-spectrin and cleaved caspase-3 immunoreactivity may be related to aging of the spinal cord in dogs. 相似文献
999.
Yoo DY Kim W Nam SM Chung JY Choi JH Yoon YS Won MH Hwang IK 《Neurochemical research》2012,37(5):1011-1018
In a previous study, we reported that the administration of pyridoxine (vitamin B6) to mice for 3 weeks significantly increased cell proliferation and neuroblast differentiation in the dentate gyrus without
any neuronal damage. In the present study, we investigated the restorative potentials of pyridoxine on ischemic damage in
the hippocampal CA1 region of Mongolian gerbils. Gerbils were subjected to 5 min of transient ischemia, and surgical operation
success was assessed by ophthalmoscope during occlusion of common carotid arteries and spontaneous motor activity at 1 day
after ischemia/reperfusion. Pyridoxine (350 mg/kg) or its vehicle (physiological saline) was intraperineally administered
to ischemic gerbils twice a day starting 4 days after ischemia/reperfusion for 30 or 60 days. The repeated administration
of pyridoxine for 30 and 60 days significantly increased doublecortin-immunoreactive neuroblasts in the dentate gyrus and
increased NeuN-immunoreactive mature neurons and βIII-tubulin-immunoreactive dendrites in the hippocampal CA1 region. Furthermore,
brain-derived neurotrophic factor (BDNF) protein levels were significantly increased in pyridoxine-treated groups compared
to those in the vehicle-treated groups. These results suggest that chronic administration of pyridoxine enhances neuroblast
differentiation in the dentate gyrus and induces new mature neurons in the hippocampal CA1 region by up-regulating BDNF expression
in hippocampal homogenates. 相似文献
1000.
Kang SH Jeong SJ Kim SH Kim JH Jung JH Koh W Kim JH Kim DK Chen CY Kim SH 《PloS one》2012,7(4):e28706