• BMB Reports
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• v.44 no.8
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• pp.517-522
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• 2011

Mitochondrial dynamics not only involves mitochondrial morphology but also mitochondrial biogenesis, mitochondrial distribution, and cell death. To identify specific regulators to mitochondria dynamics, we screened a chemical library and identified niclosamide as a potent inducer of mitochondria fission. Niclosamide promoted mitochondrial fragmentation but this was blocked by down-regulation of Drp1. Niclosamide treatment resulted in the disruption of mitochondria membrane potential and reduction of ATP levels. Moreover, niclosamide led to apoptotic cell death by caspase-3 activation. Interestingly, niclosamide also increased autophagic activity. Inhibition of autophagy suppressed niclosamide-induced cell death. Therefore, our findings suggest that niclosamide induces mitochondria fragmentation and may contribute to apoptotic and autophagic cell death.

• Animal cells and systems
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• v.12 no.1
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• pp.35-39
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• 2008

Menadione induced cell death in cultured C2 myoblasts. By screening synthetic peptide libraries composed of random sequence of hexapeptides, we identified the hexa-peptides pool of(Ala/Ile)-(Ile/Met)-Val-Ile-Asp-(Met/Ser)-$NH_2$ that protected the myoblasts against menadioneinduced cell death. Pre-incubation with the hexapeptide pool reduced the number of cells detached from culture dish substrate and increased the ratio of relative viability against menadione. In addition, the peptides strongly increased the expression of Bcl-2, an anti-apoptotic protein. These results suggest that the hexapeptides might enhance the resistance to cell death against menadione by increasing the expression of Bcl-2.

• BMB Reports
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• v.38 no.5
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• pp.619-623
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• 2005

The efficacy of chemotherapeutic agents on tumor cells has been shown to be modulated by tumor suppressor gene p53 and its target genes such as Bcl-2 family members (Bax, Noxa, and PUMA). However, various chemotherapeutic agents can induce cell death in tumor cells that do not express the functional p53, suggesting that some chemotherapeutic agents may induce cell death in a p53-independent pathway. Here we showed that etoposide can induce the similar degree of cell death in p53-deficient HCT 116 cells, whereas 5'-FU-mediated cell death is strongly dependent on the existence of functional p53 in HCT 116 cells. Further, we provide the evidence that etoposide can induce the cytochrome c release from isolated mitochondria, and etoposide-induced cytochrome c release is not accompanied with the large amplitude swelling of mitochondria. These data suggest that etoposide can directly induce the mitochondrial dysfunction irrespective of p53 status, and it may, at least in part, account for the p53-independent pathway in cell death induced by chemotherapeutic agents.

• BMB Reports
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• v.35 no.1
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• pp.54-60
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• 2002

The effects of individual cytokine on apoptosis have been extensively studied. However, the effect of the cytokine combination, or the synergistic effect of cytokines on cell death, has not been widely studied, though synergism between cytokines has been documented in a variety of biological situations. In our effort to identify the final death effector molecule(s) in autoimmune diabetes, we inadvertently became interested in the cytokine synergism. We discovered that $IFN{\gamma}/TNF{\alpha}$ synergism, rather than the Fas ligand as currently believed, is responsible for the apoptosis of pancreatic islet cells both in vitro and in vivo. We also studied similar cytokine synergism in cancer cell deaths, and noted the similarities and dissimilarities between cancer cell death and islet cell death.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.4
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• pp.265-271
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• 2012

HoxB4, a homeodomain-containing transcription factor, is involved in the expansion of hematopoietic stem cells and progenitor cells in vivo and in vitro, and plays a key role in regulating the balance between hematopoietic stem cell renewal and cell differentiation. However, the biological activity of HoxB4 in other cells has not been reported. In this study, we investigated the effect of overexpressed HoxB4 on cell survival under various conditions that induce death, using the Ba/F3 cell line. Analysis of phenotypical characteristics showed that HoxB4 overexpression in Ba/F3 cells reduced cell size, death, and proliferation rate. Moreover, the progression from early to late apoptotic stages was inhibited in Ba/F3 cells subjected to HoxB4 overexpression under removal of interleukin-3-mediated signal, leading to the induction of cell cycle arrest at the G2/M phase and attenuated cell death by Fas protein stimulation in vitro. Furthermore, apoptotic cell death induced by doxorubicin-treated G2/M phase cell-cycle arrest also decreased with HoxB4 overexpression in Ba/F3 cells. From these data, we suggest that HoxB4 may play an important role in the regulation of pro-B cell survival under various apoptotic death environments.

• Development and Reproduction
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• v.15 no.3
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• pp.205-213
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• 2011

Ethanol treatment during the brain growth spurt period has been known to induce the death of Purkinje cells. The underlying molecular mechanisms and the role of reactive oxygen species (ROS) in triggering ethanol-induced Purkinje cell death are, however, largely unresolved. We undertook TUNEL staining, western blotting assay and immunohistochemistry for the cleaved forms of caspase-3 and -9, with calbindin D28K double immunostaining to identify apoptotic Purkinje cells. The possibility of ROS-induced Purkinje cell death was immunohistochemically determined by using anti-8-hydroxy-2'deoxyguanosine (8-OHdG), a specific cellular marker for oxidative damage. The results show that Purkinje cell death of PD 5 rat cerebellum following ethanol administration is mediated by the activation of caspase-3 and -9. However, unexpectedly, TUNEL staining did not reveal any positive Purkinje cells while there were some TUNEL-positive cells in the internal and external granular layer. 8-OHdG was detected in the Purkinje cell layers at 8 h, peaked at 12-24 h, but not at 30 h post-ethanol treatment. No 8-0HdG immunoreactive cells were detected in the internal and external granular layer. The lobule specific 8-OHdG staining patterns following ethanol exposure are consistent with that of ethanol-induced Purkinje cell loss. Thus, we suggest that ethanol-induced Purkinje cell death may not occur by the classical apoptotic pathway and oxidative damage is involved in ethanol-induced Purkinje cell death in the developing cerebellum.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.2
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• pp.65-71
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• 2003

Increasing evidences suggest that ischemia-induced vascular damage is an integral step in the cascade of the cellular and molecular events initiated by cerebral ischemia. In the present study, employing a mouse brain endothelioma-derived cell line, bEnd.3, and oxygen-glucose deprivation (OGD) as an in vitro stroke model, the role of nuclear factor kappa B (NF-${\kappa}B$) activation during ischemic injury was investigated. OGD was found to activate NF-${\kappa}B$ and to induce bEnd.3 cell death in a time-dependent manner. OGD phosphorylated neither 32 Ser nor 42 Tyr of $I{\kappa}B{\alpha}$. OGD did not change the amount of $I{\kappa}B{\alpha}$. The extents of OGD-induced cell death after 8 h, 10 h, 12 h and 14 h of OGD were 10%, 35%, 60% and 85%, respectively. Reperfusion following OGD did not cause additional cell death, indicating no reperfusion injury after ischemic insult in cerebral endothelial cells. Three known as NF-${\kappa}B$ inhibitors, including pyrrolidine dithiocarbamate (PDTC) plus zinc, aspirin and caffeic acid phenethyl ester (CAPE), inhibited OGD-induced NF-${\kappa}B$ activation and increased OGD-induced bEnd.3 cell death in a dose dependent manner. There were no changes in the protein levels of bcl-2, bax and p53 which are modulated by NF-${\kappa}B$ activity. These results suggest that NF-${\kappa}B$ activation might be a protective mechanism for OGD-induced cell death in bEnd.3.

• The Journal of Korean Medicine
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• v.39 no.1
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• pp.35-43
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• 2018

Objectives: In the brain, glutamate is the most important excitable neurotransmitter in physiological and pathological conditions. However, the high level of glutamate induces neuronal cell death due to exitotoxicity and oxidative stress. The present study investigated to evaluate a possible neuroprotective effect of furosin isolated from Euphorbia helioscopia against glutamate-induced HT22 cell death. Methods: Furosin was isolated from methanol extract of Euphorbia helioscopia and examined whether it protects glutamate-induced neuronal cell death. The cell viability was determined using Ez-Cytox assay. Anti-oxidative effect of furosin was determined by DPPH scavenging activities, and the levels of intracellular reactive oxygen species (ROS) were determined by the fluorescent intensity after staining the cells with $H_2DCFDA$. To evaluate apoptotic cell death, we performed nuclear staining and image-based cytometeric analysis. Results: The cell viability was significantly increased by treatement with furosin compared with the treatment with glutamate. Furosin showed a strong DPPH radical scavenging activity ($EC50=1.83{\mu}M$) and prevented the accumulation of intra cellular ROS. Finally, the presence of 50 and $100{\mu}M$ furosin significantly the percentage of apoptotic cells compared with glutamate treatment. Conclusion: The present study found that furosin is a potent neuroprotectant against glutamate-induced oxidative stress through inhibition of apoptotic cell death induced by glutamate. Therefore, the present study suggests that furosin as a bioactive compound of E. helioscopia can be a useful source to develop a drug for the treatment of neurodegenerative diseases and acute brain injuries.

• The Korea Journal of Herbology
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• v.20 no.4
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• pp.121-132
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• 2005

Objectives : Siegesbeckiae Herba's effect on the protection of nerve cells was tested, and the effects were compared between Siegesbeckia glabrescens Makino, the state of which is spica imported from China, and original Korean leaves of it. Methods : After damaging nerve cells by exposing them on NMDA (N-methyl-D-aspartic acid) and KA(kainic acid), Siegesbeckiae Herba's effect on cell death, inhibition rate, glutamate separation, and ROS(reactive oxygen species) production were examined. Results : 1. Siegesbeckiae Herba inhibited the cell death exposed to NMDA. 2. Siegesbeckiae Herba inhibited the amount of glutamate separated from nerve cells exposed to NMDA. 3. Siegesbeckiae Herba inhibited the production of ROS induced by NMDA. 4. Siegesbeckiae Herba did not inhibit the cell death exposed to KA. 5. Chinese Siegesbeckiae Spica had no inhibition effect on cell death. Conclusions : Siegesbeckiae Herba was effective in inhibiting the death of nerve cells exposed to NMDA, and in protecting nerve cells from various damages in nerve cell diseases. Because Chinese Siegesbeckiae Spica did not show such effects, it is necessary to closely examine those effects according to the used parts.

• BMB Reports
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• v.47 no.7
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• pp.393-398
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• 2014

The role of Bax inhibitor-1 (BI-1) in the protective mechanism against apoptotic stimuli has been studied; however, as little is known about its role in death receptor-mediated cell death, this study was designed to investigate the effect of BI-1 on Fas-induced cell death, and the underlying mechanisms. HT1080 adenocarcinoma cells were cultured in high concentration of glucose media and transfected with vector alone (Neo cells) or BI-1-vector (BI-1 cells), and treated with Fas. In cell viability, apoptosis, and caspase-3 analyses, the BI-1 cells showed enhanced sensitivity to Fas. Fas significantly decreased cytosolic pH in BI-1 cells, compared with Neo cells, and this decrease correlated with BI-1 oligomerization, mitochondrial $Ca^{2+}$ accumulation, and significant inhibition of sodium-hydrogen exchanger (NHE) activity. Compared with Neo cells, a single treatment of BI-1 cells with the NHE inhibitor EIPA or siRNA against NHE significantly increased cell death, which suggests that the viability of BI-1 cells is affected by the maintenance of intracellular pH homeostasis through NHE.