• 제목, 요약, 키워드: glial cells

검색결과 261건 처리시간 0.047초

Silencer 및 DNA methylation에 의한 JC virus early promoter의 뇌교세포 특이적인 조절 (Glial Cell-specific Regulation of the JC virus Early Promoter by Silencer and DNA Methylation)

  • 김희선;우문숙
    • 약학회지
    • /
    • v.46 no.2
    • /
    • pp.143-148
    • /
    • 2002
  • The human polyomavirus JC virus is the etiologic agent of progressive multifocal leukoencephalopathy (PML). The JC virus early promoter directs cell-specific expression of the viral replication factor large T antigen, thus transcriptional regulation constitutes a major mechanism of glial tropism in PML. Here we found that pentanucleotide sequence immediately upstream of the TATA sequence functions as a cell-specific silencer in the JC virus transcription. In vitro binding studies showed that synthetic oligonucleotides spanning a pentanucleotide sequence, designated "oligo 2", interacts with nuclear proteins from non-glial cells in a cell-specific manner. Furthermore, the sequence preferentially repressed the heterologous thymidine kinase promoter activity in non-glial cells. We also tested whether JC virus transcription is controlled by DNA methylation. Transient transfection of in vitro methylated JC virus promoter abolished transcription in both the glial and non-glial cells. The repression fold was much larger in glial cells than in non-glial cells. Taken together, this finding suggests that glial cell-specific expression of the JC virus is controlled by DNA methylation as well as cell-specific silencers.

도담탕가미방(導痰湯加味方)이 tunicamycin에 의한 소포체 스트레스성 C6 glial 세포사멸에 미치는 영향 (Protective Effect of Dodamtanggami-bang on Endoplasmic Reticulum Stress in C6 Glial Cells)

  • 김봉상;문병순
    • 동의생리병리학회지
    • /
    • v.24 no.6
    • /
    • pp.1004-1011
    • /
    • 2010
  • This study was designed to evaluate the protective effects of Dodamtanggami-bang (DDTG) on tunicamycin induced cell death by ER stress in C6 glial cells. Cell viability was measured by MTT assay and LDH release. Apoptosis was determined by caspase activity and flow cytometry in C6 glial cells. Expression of ER stress mediators including, GRP78 and CHOP proteins were measured by Western blot analysis. Tunicamycin induced the apoptosis of C6 glial cells, which was characterized as nucleic acid and caspase-3 activation, PARP cleavage, and sub-G0/G1 fraction of cell cycle increase. However, pretreatment with DDTG protected C6 glial cells from tunicamycin. Treatment with tunicamycin resulted in the increased the expression of GRP78 and CHOP protein and produced ROS generation. However, pretreatment with DDTG inhibited the ER stress pathway, including increase of the expression of GRP78, CHOP proteins in C6 glial cells treated with tunicamycin. Taken together, these data suggest that DDTG is able to protect C6 glial cells from tunicamycin with marked inhibition of ER stress.

귀비탕이 Glutamate에 의한 C6 Glial Cell의 Apoptosis에 미치는 영향 (Effects of Gwibitang on Glutamate-induced Apoptosis in C6 Glial Cells)

  • 강익현;이인;한상혁;문병순
    • 대한한의학회지
    • /
    • v.22 no.4
    • /
    • pp.45-57
    • /
    • 2001
  • Objectives : The water extract of Gwibitang (GBT) has been traditionally used for treatment of psychologic disease and brain damage in Oriental Medicine, This study was designed to investigate the effect of GBT on the glutamate-induced toxicity of rat C6 glial cells. Methods : The cultured cells were pretreated with GBT and exposed to glutamate, The cell damage was assessed by using MTT assay and Hoechst, IC-l staining, Results : GBT had protective effects in glutamate-induced cytotoxicity, which was revealed as apoptosis characterized by chromatic condensation and the loss of mitochondrial membrane potential in C6 glial cells. However, GBT and glutamate had no effect in the activation of caspase family cysteine proteases including caspase-3, -8 and -9 proteasesin C6 glial ce]]s, GBT significantly recovered the depletion of GSH and inhibited the generation of $H_2O_2$ by glutamate in C6 glial cells. In addition, both GBT and antioxidants such as GSH and NAC protected the glutamate-induced cytotoxicity in C6 glial cells, indicating that GBT possibly has antioxidative effect. Moreover, GBT also inhibited the glutamate-induced degradation of $IkB{\alpha}$ in C6 glial cells, This result suggest that GBT has some inhibitory effects on the transcriptional activation of $NF-_{k}B$. Conclusions : GBT has protective effects in glutamate-induced cytotoxicity via an antioxidative mechanism.

  • PDF

Subacute Nicotine Exposure in Cultured Cerebellar Cells Increased the Release and Uptake of Glutamate

  • Lim, Dong-Koo;Park, Sun-Hee;Choi, Woo-Jeoung
    • Archives of Pharmacal Research
    • /
    • v.23 no.5
    • /
    • pp.488-494
    • /
    • 2000
  • Cerebellar granule and glial cells prepared from 7 day-old rat pups were used to investigate the effects of sub-acute nicotine exposure on the glutamatergic nervous system. These cells were exposed to nicotine in various concentrations for 2 to 10 days in situ. Nicotine-exposure did not result in any changes in cerebellar granule and glial cell viability at concentrations of up to 500 $\mu\textrm{M}$. In cerebellar granule cells, the basal extracellular levels of glutamate, aspartate and glycine were enhanced in the nicotine-exposed granule cells. In addition, the responses of N-methyl-D-aspartate (NMDA)-induced glutamate release were enhanced at low NMDA concentrations in the nicotine-exposed granule cells. However, this decreased at higher NMDA concentrations. The glutaminase activity was increased after nicotine exposure. In cerebellar glial cells, glutamate uptake in the nicotine-exposed glial cells were either increased at low nicotine exposure levels or decreased at higher levels. The inhibition of glutamate uptake by L-trans-pyrollidine-2,4-dicarboxylic acid (PDC) was lower in glial cells exposed to 50 $\mu\textrm{M}$ nicotine. Glutamine synthetase activity was lower in glial cells exposed to 100 or 500 $\mu\textrm{M}$ of nicotine. These results indicate that the properties of cerebellar granule and glial cells may alter after subacute nicotine exposure. Furthermore, they suggest that nicotine exposure during development may modulate glutamatergic nervous activity.

  • PDF

신경교세포주 C6 glial에서 Zinc의 Hydrogen Peroxide($H_2O_2$) 생성을 통한 세포고사 (Zinc-induced Apoptosis in C6 glial Cells via Generation of Hydrogen Peroxide($H_2O_2$))

  • 이지현;김명선;소흥섭;김남송;조광호;이향주;이기남;박길래
    • Toxicological Research
    • /
    • v.16 no.3
    • /
    • pp.179-185
    • /
    • 2000
  • Zinc is known to generate reactive oxygen species (ROS) including superoxide anion and hydrogen peroxide ($H_2O_2$), which eventually contribute to cytotoxicity in a variety of cell types. Here in, we demonstrated that zinc decreased the viability of C6 glial cells in a time and dose-dependent manner, which was revealed as apoptosis characterized by ladder-pattern fragmentation of genomic DNA. chromatin condensation and DNA fragmentation in Hoechst dye staining. Zinc-induced apoptosis of C6 glial cells was prevented by the addition of catalase and antioxidants including reduced glutathione (GSH), N-acetyl-L-cysteine (NAC) and pyrrolidinedithiocarbamate (PDTC). Wefurther confirmed that zinc decreased intrac-ellular levels of GSH and generated $H_2O_2$in C6 glial cells. Moreover, antioxidants also decreased the generation of zinc-induced $H_2O_2$ in C6 glial cells. These data indicated that zinc-induced the apoptotic death of C6 glial cells via generation of reactive oxygen species such as $H_2O_2$.

  • PDF

도홍사물탕(挑紅四物湯)이 C6 신경교세포의 2-DG에 의한 오토파지성 세포사멸에 미치는 영향 (Protective Effects of Dohongsamul-tang on 2-deoxy-D-glucose Induced Autophagic Cell Death in C6 Glial Cells)

  • 신학수;이성근;문병순
    • 동의생리병리학회지
    • /
    • v.23 no.3
    • /
    • pp.581-589
    • /
    • 2009
  • The water extract of Dohongsamul-tang(DHSMT) has been traditionally used in treatment of ischemic heart and brain diseases in Oriental Medicine. However, little is known about the mechanism by which DHSMT protects C6 glial cells from glucose deprevation induced damages. Therefore, this study was designed to evaluate the protective effects of DHSMT on 2-deoxy-D-glucose induced autophagy of C6 glial cells. Autophagic phenotype is evaluated by fluorescence microscopy and flow cytometry with specific biological staining dyes, including monodansylcadaverine and acridine orange, as well as Western blot analysis with microtubule-associated protein 1 light chain 3(LC3) and Beclin-1. Treatment with 2-deoxy-D-glucose significantly resulted in a decrease of the viability of C6 glial cells and increase of the extracellular LDH release in a dose and time-dependent manner. However, pretreatment with DHSMT protected C6 glial cells from glucose deprivation with 2-deoxy-D-glucose. The author also observed the fact that autophagy phenotype occurred by 2-deoxy-D-glucose in C6 glial cells. Pretreatment with 3-MA, a pharmacological inhibitior of autophagy, abolished the formation of acidic vesicle organelle in C6 glial cells treated with 2-deoxy-D-glucose. However, pretreatment with DHSMT inhibited the formation of autophagic phenotypes, including formation of acidic vesicle organelle, and increase of the expression of LC-3 II Beclin-1 proteins in C6 glial cells treated with 2-deoxy-D-glucose. Taken together, these data suggest that DHSMT is able to protect C6 glial cells from glucose deprivation with marked inhibition of autophagy formation.

Phagocytic Roles of Glial Cells in Healthy and Diseased Brains

  • Jung, Yeon-Joo;Chung, Won-Suk
    • Biomolecules & Therapeutics
    • /
    • v.26 no.4
    • /
    • pp.350-357
    • /
    • 2018
  • Glial cells are receiving much attention since they have been recognized as important regulators of many aspects of brain function and disease. Recent evidence has revealed that two different glial cells, astrocytes and microglia, control synapse elimination under normal and pathological conditions via phagocytosis. Astrocytes use the MEGF10 and MERTK phagocytic pathways, and microglia use the classical complement pathway to recognize and eliminate unwanted synapses. Notably, glial phagocytosis also contributes to the clearance of disease-specific protein aggregates, such as ${\beta}$-amyloid, huntingtin, and ${\alpha}$-synuclein. Here we reivew recent findings showing that glial cells are active regulators in brain functions through phagocytosis and that changes in glial phagocytosis contribute to the pathogenesis of various neurodegenerative diseases. A better understanding of the cellular and molecular mechanisms of glial phagocytosis in healthy and diseased brains will greatly improve our current approach in treating these diseases.

소풍탕(疎風湯)이 Glutamate에 의한 C6 Glial Cell의 Apoptosis에 미치는 영향 (Effect of Sopung-tang on Glutamate-Induced Apoptosis in C6 Glial Cells)

  • 정승원;최철원;김봉상;문병순
    • 동의생리병리학회지
    • /
    • v.22 no.6
    • /
    • pp.1423-1430
    • /
    • 2008
  • The water extract of Sopung-tang(SPT) has been traditionally used for treatment of psycologic disease and brain damage in oriental medicine. However, little is known about the mechanism by which the water extract of SPT rescues cells from these disease. Therefore, this study was designed to investigate the effect of SPT on the glutamate-induced toxicity of rat C6 glial cells. SPT have protective effects in glutamate-induced toxicity, which was revealed as apoptosis characterized by chromatic condensation and fragmentation and the loss of mitochondrial membrane potential in C6 glial cells. Also, SPT have inhibited the active form of caspase-3 and PARP and significantly protected the apoptotic phenomena by glutamate toxicity in C6 glial cells. However, SPT significantly recovered the depletion of GSH and inhibited the generation of ROS by glutamate in C6 glial cells. In addition, both SPT and antioxidants such as GSH and NAC protected the glutamate-induced cytotoxicity in C6 glial cells, indicating that SPT possibly have antioxidative effect. Specially, SPT were showed transcriptional factor significantly increased the activation of NF-${\kappa}B$ using the analysis of NF-${\kappa}B$ luciferase reporter system in C6 glial cells. These NF-${\kappa}B$ activation protected cells from glutamate-induced toxicity to generate the heme oxygenase-1(HO-1). Taken together, we suggest that SPT have protective effects in glutamate-induced toxicity via a antioxidative mechanism.

대칠기탕(大七氣湯)이 Glutamate에 의한 C6 Glial 세포의 Apoptosis에 미치는 영향 (Effects of Daechilgi-tang on Glutamate-induced Apoptosis in C6 Glial Cells)

  • 김혜윤;고석재;방창호;신선호;이동엽;이인
    • 대한한방내과학회지
    • /
    • v.31 no.4
    • /
    • pp.693-705
    • /
    • 2010
  • Objectives : The water extract of Daechilgi-tang(DCGT) has traditionally been used for treatment of qi stagnation(氣滯), which is considered to be one of the important causes of neuronal disease in oriental medicine. However, little is known about the mechanism by which DCGT protects neuronal cells from brain cell damages. Methods and Results : The author tested the mechanism of the cytoprotective effect of DCGT on glutamate -stimulated rat C6 glial cells. DCGT significantly protected C6 glial cells from glutamate in MTT assay. Pre-treatment of C6 glial cells with DCGT markedly inhibited the DNA fragmentation of C6 cells induced by glutamate. Glutamate increased the generation of reactive oxygen species(ROS) and intracellular calcium level in C6 glial cells. However, pre-treatment with DCGT markedly suppressed the increase of ROS generation and intracellular calcium accumulation induced by glutamate. Among apoptosis signaling mediators, DCGT markedly increased the expression level of Bcl2 in glutamate-treated cells. It also inhibited the cleavage of caspase-3 and PARP proteins by glutamate in C6 glial cells. Conclusions : These results suggest that DCGT protects brain cells from glutamate cytotoxicity through inhibition of ROS generation and activation of apoptosis signaling pathway as well as induction of the anti-oxidant system.

신경아교세포와 조현병 (Neuroglial Cells and Schizophrenia)

  • 원승희
    • 생물정신의학
    • /
    • v.22 no.2
    • /
    • pp.47-54
    • /
    • 2015
  • In the past decade, structural, molecular, and functional changes in glial cells have become a major focus in the search for the neurobiological foundations of schizophrenia. Glial cells, consisting of oligodendrocytes, astrocytes, microglia, and nerve/glial antigen 2-positive cells, constitute a major cell population in the central nervous system. There is accumulating evidence of reduced numbers of oligodendrocytes and altered expression of myelin/oligodendrocyte-related genes that might explain the white matter abnormalities and altered inter- and intra-hemispheric connectivities that are characteristic signs of schizophrenia. Astrocytes play a key role in the synaptic metabolism of neurotransmitters ; thus, astrocyte dysfunction may contribute to certain aspects of altered neurotransmission in schizophrenia. Increased densities of microglial cells and aberrant expression of microglia-related surface markers in schizophrenia suggest that immunological/inflammatory factors are of considerable relevance to the pathophysiology of psychosis. This review describes current evidence for the multifaceted role of glial cells in schizophrenia and discusses efforts to develop glia-directed therapies for the treatment of the disease.