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한국인 편두통 및 허혈성 뇌졸중 환자에서 C677T MTHFR 유전자의 다형성
김병건,김만호,강라미,배희준,구자성,권오현,이종은,이상수 대한신경과학회 2005 대한신경과학회지 Vol.23 No.2
Background: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism has been implicated in both migraine and ischemic stroke. The homozygous C677T mutation in the MTHFR gene was more frequent in the Japanese and Turkish migraineurs than in the control group. Positive associations have also been found in ischemic stroke. The purpose of this study is to investigate the role of MTHFR C677T polymorphism in Korean patients with migraine or ischemic stroke. Methods: We analyzed the allele frequencies and genotype of MTHFR C677T polymorphism in 115 patients with migraine, 213 with cerebral infarction, and 73 controls. Results: There was no significantly increased frequency of homozygosity for the T677 allele in both of the diagnostic groups, compared to the controls. Conclusions: Our results suggest that MTHFR gene C677T polymorphism is unlikely to play a major role in the pathogenesis of migraine or ischemic stroke in Korean patients.
Heat shock protein 70 alters the endosome-lysosomallocalization of huntingtin
강봉선,안진영,김민기,김현정,강라미,임헌창,박경숙,이재선,서정선,차중익,김승업,박유정,김만호 생화학분자생물학회 2007 Experimental and molecular medicine Vol.39 No.1
Huntingtons disease is caused by CAG trinucleotide expansions in the gene encoding huntingtin. N- terminal fragments of huntingtin with polyglu-tamine produce aggregates in the endosome-ly-sosomal system, where proteolytic fragments of huntingtin is generated. Heat shock protein 70 (HSP70) prevents the formation of protein aggre-gates, but the effect of HSP70 on the huntingtin in the endosome-lysosomal system is unknown. This study was to determine whether HSP70 alters the distribution of huntingtin in endosome-lysosomal system. HSP70 expressing stable cells (NIH/3T3 or cerebral hybrid cell line A1) were generated, and mutant [(CAG)100] huntingtin was transiently over-expressed. Analysis of subcellular distribution by immnuocytochemistry or proteolysis cleavage by Western blotting was performed. 18 CAG repeat wild type [WT; (CAG)18] huntingtin was used as a control. Cells with huntingtin showed paterns of endosome- lysosomal accumulation, from a dispersed vacuole (DV) type into a coalescent perinuclear vacuole (PV) type over time. In WT huntingtin, HSP70 increased the cells with the PV types that enhanced the proteolytic cleavage of huntingtin. However, HSP70 reduced cells of the DV and PV types expressing mutant ess proteolysis than that of control. In addition, intranuclear inclusions were formed only in mutant cells, which was no t affected by HSP70. These results suggest that HSP70 alters the distribution of huntingtin in the endosome- lysosomal system, and that this contributes to huntingtin proteolysis.
홍삼추출액의 인간성체신경줄기세포 증식과 세포사 관련 세포주기의 변화에 대한 효과
김현정(Hyun-Jung Kim),강라미(Lami Kang),안진영(Jin Young Ahn),한정순(Jung Soon Han),김승업(Seung U. Kim),이광우(Kwang-Woo Lee),김만호(Manho Kim) 고려인삼학회 2004 Journal of Ginseng Research Vol.28 No.1
홍삼추출액의 신경성체줄기세포 성장과 생존에 미치는 영향을 분석하고자 human neuronal stem cell line인 F3 cell을 배양한 후 홍삼추출액을 여러 농도로 희석하여 MTT assay로 cell viability를 측정하였고 FACS analysis로 cell cycle변화를 측정하였다. 특정한 농도에서는 세포가 증식되는 경향을 보였으며 농도가 증가되면서 viability가 감소되는 현상을 확인할 수 있었다. Cell cycle분석상 세포증식시에는 S phase 및 G2/M phase가 증가되는 경향을 보였고, viability가 감소되면서 S phase가 감소되고 G0/G1 phase가 증가되었다. 한편 DNA fragmentation이 cell viability감소에 따라 증가되었으나, Caspase 3 activation 또는 Bax expression과는 관련성이 적었다. The present study is to determine whether the Red-ginseng extract has a proliferative or cytotoxic effect on the human neuronal stem cells(hNSCs). The hNSCs were grown and incubated with different doses of Red-ginseng extract. We tested the proliferative or cytotoxic effects by MTT and FACS analysis. Cell viability, cell cycle analysis, DNA fragmentation, and bax or PARP expressions were evaluated. The hNSCs showed a proliferatve trend with its peak concentration at 0.3㎍/㎖. Beyond this point, higher doses decreased viabilities and showed a cytotoxic effect at 10㎍/㎖. There was a tendency of increased S and G2/M phases during cell proliferation. In a cytotoxic condition, decreased S phase and increased G0/G1 phases were noted, suggesting cell cycle arrest. The cytotoxic effect was associated with increase DNA fragmentation in a dose-dependent manner. However, PARP cleavage or bax expression was not detected. Our results suggest that Red-ginseng extract has dual effects, the cell proliferative or cytotoxic effect, on hNSCs in vitro with dose-dependent manner.