• Title, Summary, Keyword: glial cells

Search Result 261, Processing Time 0.031 seconds

Protective Effect of Palmul-tang on Glutamate Induced Cytotoxicity in C6 Glial cells (Glutamate로 유도된 C6 glial 세포의 독성에 대한 팔물탕(八物湯)의 보호 효과)

  • Shin, Yong-Jeen;Shin, Sun-Ho
    • Journal of Physiology & Pathology in Korean Medicine
    • /
    • v.26 no.4
    • /
    • pp.475-482
    • /
    • 2012
  • This study was designed to elucidate the mechanism of the cytoprotective effect of the Palmul-tang (PMT) on glutamate induced cytotoxicity in rat C6 glial cells. We determined the increase of cell viability by PMT on glutamate-induced death of C6 glial cell. On some experiments, glutamate induced cell death to be an apoptotic phenomena characterized by G1 arrest in cell cycle, chromatin condensation, DNA fragmentation in C6 glial cells. However, pre-treatment of PMT inhibited characteristic apoptotic phenomena. One of the main mediator of glutamate-induced cytotoxicity was known to generation of reactive oxigen species. In this study, PMT attenuated generation of reactive oxigen species by glutamate through down-regulation of NOX1 expression in C6 glial cells. Furthermore, PMT regulated Bcl2 families and caspase proteins, which contribute the cell survival or death. This study suggests that PMT may be candidate for both of therapeutic and protective prescription.

Effects of Chronic Lead Exposure on Glutamate Release and Uptake in Cerebellar Cells of Rat Pups

  • Yi, Eun-Young;Lim, Dong-Koo
    • Archives of Pharmacal Research
    • /
    • v.21 no.2
    • /
    • pp.113-119
    • /
    • 1998
  • Changes in the release and uptake of glutamate in cerebellar granule and glial cells of offspring of lead-exposed mothers were determined. In cultured cerebellar granule cells exposed to lead for 5 days, glutamate release was less influenced upon N-methyl-D-aspartate (NMDA) stimulation than that in the control. Although the NMDA-stimulated release of glutamate in cerebellar granule cells prepared from lead-exposed first generation pups was not different from that of the control group, the S-nitroso-N-acetylpenicillamine (SNAP)-stimulated release of glutamate in cerebellar granule cells obtained from lead-treated pups was less elevated than that in the control. Furthermore, in cerebellar granule cells obtained from lead-exposed second generations pups, glutamate release did not respond to both NMDA and SNAP stimulation. In cerebellar glial cells exposed to lead, the basal glutamate uptake was not changed. However, the L-trans-pyrollidine-2,4-dicarboxylic acid (PDC)-blocking effects was significantly reduced. In glial cells obtained from lead-exposed pups, the glutamate uptake was also less blocked by PDC than that in the control. Further decreases in PDC-blocking effects were observed in cerebellar glial cells obtained from lead-treated second generation pups compared to those from the control group. These results indicate that lead exposure induces the changes in the sensitivities of the glutamate release and uptake transporter. In addition, these results suggest that lead exposure might affect the intracellular signalling pathway and transmission in glutamatergic nervous system.

  • PDF

Effects of Samul-tang on Nitric Oxide Induced-cytotoxicity in C6 Glial Cell (Nitric Oxide에 의해 유발된 C6 glial 세포독성(細胞毒性)에 대한 사물탕(四物湯)의 방어효과(防禦效果))

  • Kim, Do-Hwan;Kim, Seung-Mo;Cho, Han-Gook;Cha, Yong-Seok;Heo, Yun;Cho, Kwang-Ho;Moon, Byung-Soon
    • The Journal of Internal Korean Medicine
    • /
    • v.21 no.4
    • /
    • pp.535-542
    • /
    • 2000
  • The water extracts of Samul-tang(SMT) has been used for treatment of ischemic brain damage in Oriental traditional medicine. However, little is known about the mechanism by which the water extracts of SMT rescues brain cells from ischemic damages. To elucidate the protective mechanism on ischemic induced cytotoxicity, I investigate the regulation of LPS and PMA induced iNOS expression in C6 glial cells. LPS and PMA treatment for 72 h in C6 glial cells markedly induce nitric oxide(NO), but treatment of the cells with the water extracts of SMT decrease. dose dependently nitrite formation. In addition, LPS and PMA treatment for 72 h induce severe cell death and LDH release in C6 glial cells. However treatment of the cells with the water extracts of SMT dose not induce significant changes compare to control cells. Furthermore, the protective effects of the water extracts of SMT is mimicked by treatment of $N^{G}MMA$, a specific inhibitor of NOS. LPS and PMA induced iNOS activation in C6 glial cells cause chromosomal condensation and fragmentation of nuclei by caspase activation. The treatment of the cells with the water extracts of SMT may suppress apoptosis via caspase inhibition by regulation of iNOS expression. Taken together, I suggest that the protective effects of the water extracts of SMT against ischemic brain damages may be mediated by regulation of iNOS during ischemic condition.

  • PDF

Protective Effects of Ukyium(우귀음, Yougui-yin) in Zinc-induced Apoptosis of C6 Glial Cells (우귀음이 Zinc에 의한 신경교세포의 고사(Apoptosis)에 미치는 영향)

  • 이영구;문병순
    • The Journal of Korean Medicine
    • /
    • v.22 no.3
    • /
    • pp.63-73
    • /
    • 2001
  • Objectives : The objective of the current study is to determine the protective effect of Ukyium(Yougui-yin) on the apoptosis induced by zinc. Methods : Zinc is known to generate reactive oxygen species (ROS), including superoxide anion ($O_2$) and hydrogen peroxide ($H_2O_2$), which eventually contribute to cytotoxicity in a variety of cell types. We investigated the viablity of cells, $H_2O_2$ generation, chromatin condensation and nuclear fragmentation in Hoechst dye staining and $IkB-{\alpha}$ degradation in C6 glial cells of $ZnCl_2$ between pretreatment- and not pretreatment-group with Ukyium. The former methods were researched by Time- and Dose-dependent manners. Results : We demonstrated that pretreatment with Ukyium prevented zinc-induced cell death of C6 glial cells and apoptotic characteristics including chromatin condensation and nuclear fragmentation. Ukyium also prevented $H_2O_2-induced$ cell death. We further confirmed that Ukyium decreased zinc-induced generation of $H_2O_2$ and inhibited degradation of $IkB-{\alpha}$ by zinc in C6 glial ceHs. Conclusions : These data indicated that Ukyium (Yougui-yin) prevents zinc-induced apoptotic death of C6 glial cells via inhibition of ROS generation, such as $H_2O_2$ as well as inhibition of $IkB-{\alpha}$ degradation.

  • PDF

Lead increases Nitric Oxide Production in Immunostimulated Glial Cells

  • Choi, Min-Sik;Shin, Chan-Young;Ryu, Jae-Ryun;Lee, Woo-Jong;Cheong, Jae-Hoon;Choi, Chang-Rak;Kim, Won-Ki;Ko, Kwang-Ho
    • Biomolecules & Therapeutics
    • /
    • v.12 no.4
    • /
    • pp.209-214
    • /
    • 2004
  • Lead has long been considered as a toxic environmental pollutant that severely damages the central nervous system. In various neurogenerative diseases, actrocytes become activated by proinflammatory cytokines. In the present study, we investigated whether lead (Pb$^{2+}$) affects inducible nitric oxide synthase (iNOS) expression in activated glial cells. Rat primary glial cells were stimulated with lipopolysaccharide (LPS, 1 ${\mu}$g/ml) plus IFN$_{\gamma}$(100 U/ml). Pre-treatment of Pb$^{2+}$ increased nitric oxide (NO) production in LPS/IFN$_{\gamma}$-stimulated glial cells. Lead itself, however, suppressed the basal production of NO in control glial cells. Addition of the iNOS inhibitors L-NAME (1 mM) and L-NNA (800 ${\mu}$M) prevented the Pb$^{2+}$-induced increase in NO production. Western blot analysis showed that pre-treatment of Pb$^{2+}$ augmented LPS/IFN$_{\gamma}$-induced increase in iNOS immunoreactivity, which was well correlated with the increased NO production. In addition, pre-treatment of Pb$^{2+}$ synergistically increased the iNOS mRNA expression induced by LPS and IFN${\gamma}$. The present results indicate that lead intoxication adversely affect brain function by potentiating iNOS expression and NO production in activated glial cells observed in various neurodegenerative diseases.

The Protective Effects of Insulin on Hydrogen Peroxide-Induced Oxidative Stress in C6 Glial Cells

  • Mahesh, Ramalingam;Kim, Sung-Jin
    • Biomolecules & Therapeutics
    • /
    • v.17 no.4
    • /
    • pp.395-402
    • /
    • 2009
  • Insulin appears to play a role in brain physiology, and disturbances of cerebral insulin signalling and glucose homeostasis are implicated in brain pathology. The objective of the present study was to investigate the protective effects of insulin under conditions of oxidative stress induced by hydrogen peroxide ($H_2O_2$) in C6 glial cells. Insulin at concentration of $10^{-7}$ M could prevent 12 h $H_2O_2$-induced cell death. The formation of reactive oxygen species (ROS), nitric oxide (NO) and 2-thiobarbituric acid-reactive substances (TBARS) were significantly scavenged by insulin pre-treatment in C6 glial cells after $H_2O_2$-induced oxidative stress. Insulin significantly stimulated the phosphorylation of Akt in the cells and the activation of Akt was maintained in response to insulin under $H_2O_2$ incubation for 12 h. In conclusion, these results provide evidence that insulin acts as a free radical scavenger and stimulating Akt activity. These data suggest that insulin may be effective in degenerative diseases with oxidative stress.

Anthocyanin Extracts from Black Soybean (Glycine max L.) Protect Human Glial Cells Against Oxygen-Glucose Deprivation by Promoting Autophagy

  • Kim, Yong-Kwan;Yoon, Hye-Hyeon;Lee, Young-Dae;Youn, Dong-Ye;Ha, Tae-Joung;Kim, Ho-Shik;Lee, Jeong-Hwa
    • Biomolecules & Therapeutics
    • /
    • v.20 no.1
    • /
    • pp.68-74
    • /
    • 2012
  • Anthocyanins have received growing attention as dietary antioxidants for the prevention of oxidative damage. Astrocytes, which are specialized glial cells, exert numerous essential, complex functions in both healthy and diseased central nervous system (CNS) through a process known as reactive astrogilosis. Therefore, the maintenance of glial cell viability may be important because of its role as a key modulator of neuropathological events. The aim of this study was to investigate the effect of anthocyanin on the survival of glial cells exposed to oxidative stress. Our results demonstrated that anthocyanin extracts from black soybean increased survival of U87 glioma cells in a dose dependent manner upon oxygen-glucose deprivation (OGD), accompanied by decrease levels of reactive oxygen species (ROS). While treatment cells with anthocyanin extracts or OGD stress individually activated autophagy induction, the effect was signifi cantly augmented by pretreatment cells with anthocyanin extracts prior to OGD. The contribution of autophagy induction to the protective effects of anthocyanin was verifi ed by the observation that silencing the Atg5 expression, an essential regulator of autophagy induction, reversed the cytoprotective effect of anthocyanin extracts against OGD stress. Treatment of U87 cells with rapamycin, an autophagy inducer, increased cell survival upon OGD stress comparable to anthocyanin, indicating that autophagy functions as a survival mechanism against oxidative stress-induced cytotoxicity in glial cells. Our results, therefore, provide a rationale for the use of anthocyanin as a preventive agent for brain dysfunction caused by oxidative damage, such as a stroke.

Effect of Yukgunja-tang on Glutamate-induced Apoptosis in C6 Glial Cells (육군자탕(六君子湯)이 Glutamate에 의한 C6 신경교세포의 Apoptosis에 미치는 영향)

  • Jang, Won-Seok;Shin, Yong-Jeen;Ko, Seok-Jae;Ha, Ye-Jin;Kwon, Young-Mi;Shin, Sun-Ho
    • The Journal of Internal Korean Medicine
    • /
    • v.31 no.3
    • /
    • pp.586-599
    • /
    • 2010
  • Objective : The water extract of Yukgunja-tang(YGJT) has been traditionally used in treatment of qi deficiency and phlegm in Oriental medicine. However, little is known about the mechanism by which YGJT protects neuronal cells from injury damages. Therefore, this study was designed to evaluate the protective effects of YGJT on C6 glial cells by glutamate-induced cell death. Methods : The present study describes glutamate, which is known as an excitatory neurotransmitter, related with oxidative damages, and YGJT, which shows protective effects against glutamate-induced C6 glial cell death. One of the main mediators of glutamate-induced cytotoxicity was known on the generation of reactive oxygen species(ROS) via activation of NADPH oxidase (NOX). The protective effects of antioxidant(NAC) and NOX inhibitor(apocynin) on the glutamate-induced C6 glial cells were determined by a MTT reduction assay. Result : YGJT inhibited glutamate-induced ROS generation via inhibition of NOX expression on glutamate-stimulated C6 glial cells. Furthermore, YGJT attenuated glutamate-induced caspase activation. These results suggest that YGJT could be a new potential candidate against glutamate-induced oxidative stress and cell death. Conclusion : These findings indicate that in C6 glial cells, ROS plays an important role of glutamate-induced cell death and that YGJT may prevent cell death from glutamate-induced cell death by inhibiting the ROS generation.

Effect of Cytokines on the Growth and Differentiation of the Glial Cells from Rat Brain in Culture (랫트 배양 신경교세포의 성장 및 분화에 대한 Cytokine의 효과)

  • Kim, Hae-Kyoung;Youn, Yong-Ha;Kang, Shin-Chung;Park, Chan-Woong;Kim, Yong-Sik
    • The Korean Journal of Pharmacology
    • /
    • v.32 no.2
    • /
    • pp.177-188
    • /
    • 1996
  • The effects of cytokines on the growth and differentiation of glial cells in culture were evaluated to confirm that cytokines could modify the number and function of glial cells. Proliferation of glial cells was determined by the $^3H-thymidine$ uptake and the double immunostain with anti-cell specific marker and anti-bromodeoxyuridine(BrdU) antibody. To check the effect on the differentiation of glial cells, the amount of glial fibrillar acidic protein(GFAP) and the activity of glutamine synthetase(GS) were measured in astrocytes. And also the amounts of myelin basic protein(MBP) and the activity of 2',3'-cyclic nucleotide phosphohydrolase(CNPase) were measured in oligodendrocytes. Among the cytokines used, only interleukin-$1{\beta}(IL-1{\beta})$ stimulated the growth of type 1 and type 2 astrocyte as well as 0-2A precursor cell. When the functional changes in these glial cells by cytokines were tested, $IL-1{\beta}$ did not increase GFAP content in type 1 and type 2 astrocyte, but $IL-1{\beta}$ increased GS activity in type 1 astrocyte, and slightly decreased this enzyme activity in type 2 astrocyte. Also interleukin-2(IL-2) and $interferon-{\gamma}$ $(IFN-{\gamma})$ inhibited the activity of GS in type 1 and type 2 astrocyte. On the other hand, all cytokines used did not modify the growth and differentiation in oligodendrocytes. From these results we could suggest that $IL-1{\beta}$ increases the growth of type 1 and type 2 astrocyte and also promotes the development for 0-2A precursor cell to type 2 astrocyte.

  • PDF

The effect of lead on matrix metalloproteinase-9 expression in rat primary glial cells

  • Park, Min-Sik;Lee, Woo-Jong;Kim, Young-Eun;Ko, Kwang-Ho
    • Proceedings of the Korean Society of Applied Pharmacology
    • /
    • /
    • pp.84-84
    • /
    • 2003
  • Lead has long been considered as a toxic environmental pollutant, which severely damages central nervous system. Lead can cause hypo- and de-myelination, and glial cells are closely related with myelination or demyelination. Matrix metalloproteinases (MMPs) are proteolytic enzymes that are involved in the remodelling of the extracellular matrix in a variety of physiological and pathological processes. MMPs also seem to be important in the pathogenesis of inflammatory demyelinating diseases of the central and peripheral nervous system. In this study, we investigated whether lead affects MMP-9 expression in rat primary glial cells. Treatment of 0.1-5 ${\mu}$M lead dose- and time-dependently increased MMP-9 expression in rat primary glial cells. The activity of MMPs was determined using zymography. Lead activated Erk(1/2) but neither of the other endogenous MAP kinases, p38 or JNK. Inhibition of Erk(1/2) activation by PD98059, a MEK inihibitor, prevented lead-induced expression of MMP-9. The results of the present study suggest that lead intoxication may adversely affect brain function at least in part by inducing MMP-9 expression through Erk(1/2) activation in primary glial cells.

  • PDF