• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.6
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• pp.1462-1469
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• 2008

The purpose of the study was to confirm what effect HRHDT treatment had on cell extinction by damage of endoplasmic reticulum induced to PC-12 cell damage by glucose deprivation. The study confirmed what effect it had on forming the condition of glucose deprivation within a culture fluid of PC-12 cell and on a nerve cell's survival rates and tested whether HRHDT could prevent extinction of PC-12 cell by glucose deprivation. Also, the study confirmed what effect HRHDT treatment had on the emitted quantity of LDH by glucose deprivation. To examine PC-12 cell's behavioral change under the condition of glucose deprivation and a protective effect of HRHDT on the change, the study observed PC-12 cell's behavioral change with a microscope. Also, the study confirmed density of calcium ion within cells followed by a culture time in the condition of glucose deprivation with FACS and confirmed what effect HRHDT treatment had on the above density of calcium ion within cells. Finally, the study carried out the western blot and confirmed what effect HRHDT treatment had on revelation of GRP 78 and CHOP protein and a segmental type of aspase 12. In this study, HRHDT rescued PC-12 cells from glucose deprivation-induced cell death. HRHDT also prevents the LDH release, Ca++ accumulation, and morphological change, which was associated with the ER stress. Furthermore, HRHDT reduced the expression of ER chaperone (Grp78 and CHOP) proteins by glucose deprivation in PC-12 cells. These results suggest that HRHDT might provide a useful therapeutic strategy in treatment of the neurodegenerative diseases caused by glucose deprivation injuries.

• Toxicological Research
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• v.14 no.4
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• pp.483-488
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• 1998

During cerebral ischemia two important factors such as hypoxia and reduction of glucose can act as modulating stressor affecting the release of amine neurotransmitters including 5-hydroxytryptamine (5-HT). This study was performed to investigate the effect of glucose deprivation on the oxygen deprivation-induced changes of [3H]-5-HT release in the rat hippocampal slices. Experimental groups were divided into 4 groups for this study: normoxic/normoglycemic group, oxygen-deprived group, glucose-deprived group, and oxygen/glucose-deprived group. The hippocampus of rat brain was sliced by 400 $\mu\textrm{m}$ thickness with manual chopper. After 30 minutes preincubation in the normal buffer, the slices were incubated for 20 min in buffer containing [3H]-5-HT (0.1 M, 74 $\mu\textrm$Ci) for uptake. To measure the release of [3H]-5-HT into the buffer, the incubation medium was drained of and refilled with fresh buffer every ten minutes through a sequence of 14 tubes. Oxygen deprivation by gassing with 95% $N_2$/5% $CO_2$ and/or glucose deprivation was done in the 6th and 7th tube. The radioactivities in each buffer and the tissue were counted using scintillation counter. The results were expressed as fractional release. When slices were exposed to oxygen-deprived media for 20 min, the diminution followed by the rebound release of [3H]-5-HT was observed during the post-oxygen deprived period. However, glucose deprivation or oxygen/glucose deprivation markedly increased the release of [3H]-5-HT. which was opposite to the pattern observed in oxygen-deprived group. These results suggested that oxygen deprivation itself inhibits [3H]-5-HT release in rat hippocampal slices during oxygen-deprived period, but additional glucose deprivation convert the inhibitory response to increase of [3H]-5-HT release.

• The Journal of Korean Medicine
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• v.31 no.2
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• pp.1-18
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• 2010

Objective: The water extract of Chilgi-tang (CGT) has been traditionally used in treatment of heart diseases caused by stress in Oriental Medicine. However, little is known about the mechanism by which CGT rescues neuronal cells from injury damage. Therefore, this study was designed to evaluate the protective effects of CGT on Neuro-2A cells by glucose deprivation-induced cell death. Methods: We investigated how cell death induced by glucose deprivation was associated with increased reactive oxygen species (ROS) generation. Result: The CGT treatment prior to glucose deprivation insult significantly reduced the number of cell deaths and the glucose deprivation-induced increase in ROS. Nitric oxide (NO) was also attenuated by CGT treatment. In addition, we demonstrated that the anti-cell death effect of CGT was blocked by heme oxygenase-1 (HO-1) activation. Finally, pretreatment of cells with a hemin, HO-1 inducer, reduced glucose deprivation-induced cell death. In contrast, pretreatment of cells with a ZnPP, HO-1 activity inhibitor, attenuated CGT-induced inhibition of cell death. Conclusions: These findings indicate that ROS plays an important role in glucose deprivation-induced cell death and that CGT may prevent glucose deprivation-induced cell death by inhibiting the ROS generation through HO-1 activation in Neuro-2A cells.

• Archives of Pharmacal Research
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• v.28 no.8
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• pp.942-947
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• 2005

Peroxynitrite is a potent neurotoxic molecule produced from a reaction between NO and super-oxide and induces NO-mediated inflammation under neuropathological conditions. Previously, we reported that glucose deprivation induced ATP depletion and cell death in immunostimulated astrocytes, which was mainly due to peroxynitrite. In this study, the role of MAPKs (ERK1/2, p38MAPK, and JNK/SAPK) signal pathway in the SIN-1/glucose deprivation-induced death of astrocytes was examined. A combined treatment with glucose deprivation and $50 {\mu}M$ SIN-1, an endogenous peroxynitrite generator, rapidly and markedly increased the death in rat primary astrocytes. Also, SIN-1/glucose deprivation resulted in the activation of MAPKs, which was significantly blocked by the treatment with $20{\mu}M$ MAPKs inhibitors (ERK1/2, PD98059; p38MAPK, SB203580; JNK/SAPK, SP600125). Interestingly, SIN-1/glucose deprivation caused the loss of intracellular ATP level, which was significantly reversed by MAPKs inhibitors. These results suggest that the activation of MAPKs plays an important role in SIN-1/glucose deprivation-induced cell death by regulating the intracellular ATP level.

• Journal of Microbiology and Biotechnology
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• v.30 no.5
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• pp.733-738
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• 2020

Glucose deprivation and hypoxia frequently occur in solid tumor cells, including pancreatic cancer cells. Glucose deprivation activates the unfolded protein response (UPR) and causes the up-regulation of glucose-regulated protein 78 (GRP78). Induction of GRP78 has been shown to protect cancer cells. Therefore, shutting down of GRP78 expression may be a novel strategy in anticancer drug development. Based on this understanding, a screening system established for anticancer agents that exhibit selective cytotoxicity on pancreatic cancer cells under glucose-deprived conditions. To test this hypothesis, the new compounds isolated, pancastatin A (PST-A) and B (PST-B), from Ponciri Fructus. PST-A and B were identified as glabretal triterpenoid moieties by electrospray ionization mass spectrometry and nuclear magnetic resonance spectroscopic methods. PST-A and B suppressed the accumulation of the UPR hallmark gene, GRP78, during glucose deprivation. Furthermore, PST-A and B showed selective cytotoxicity on PANC-1 pancreatic cancer cells under glucose deprivation. Interestingly, PST-A and B had no effect on these cells under normal growth conditions. Our results suggest that PST-A and B act as novel therapeutic agents to induce selective cell death in glucose-deprived pancreatic cancer cells.

• Biomolecules & Therapeutics
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• v.12 no.1
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• pp.25-33
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• 2004

In this study we investigated whether ATP loss was involved in the potentiated death of immunostimulated rat primary astrocytes in glucose-deprived condition. Rat primary astrocytes immunostimulated with LPS plus IFN-${\gamma}$ for 48 h underwent death upon glucose deprivation, which dependent on the production of peroxynitrite. Intracellular ATP level synergistically decreased by glucose deprivation in immunostimulated astrocytes but not in control cells, and the loss of ATP occurred well ahead of the LDH release. The synergistic cell death and ATP loss by immunostimulation and glucose deprivation were inhibited by iNOS inhibitor (L-NAME and L-NNA) or peroxynitrite decomposition catalyst (also a superoxide anion scavenger), Mn(III)tetrakis(N-methyl-4'-pyridyl)porphyrin (MnTMPyP). Exogenous addition of peroxynitrite generator, SIN-l timedependently induced ATP loss and cell death in the glucose-deprived astrocytes. Depletion of intracellular glutathione (GSH) and dis겨ption of mitochondrial transmembrane potential (MTP) were also observed under same conditions. Supply cellular ATP by the addition of exogenous adenosine or ATP during glucose deprivation inhibited ATP depletion, GSH depletion, MTP disruption and cell death in SIN-l treated or immunostimulated astrocytes. This study showed that perturbation in the regulation of intracellular ATP level in immunostimulated astrocytes might make them more vulnerable to energy challenging stimuli.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.2
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• pp.173-183
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• 2020

An in vitro model for ischemia/reperfusion injury has not been well-established. We hypothesized that this failure may be caused by serum deprivation, the use of glutamine-containing media, and absence of acidosis. Cell viability of H9c2 cells was significantly decreased by serum deprivation. In this condition, reperfusion damage was not observed even after simulating severe ischemia. However, when cells were cultured under 10% dialyzed FBS, cell viability was less affected compared to cells cultured under serum deprivation and reperfusion damage was observed after hypoxia for 24 h. Reperfusion damage after glucose or glutamine deprivation under hypoxia was not significantly different from that after hypoxia only. However, with both glucose and glutamine deprivation, reperfusion damage was significantly increased. After hypoxia with lactic acidosis, reperfusion damage was comparable with that after hypoxia with glucose and glutamine deprivation. Although high-passage H9c2 cells were more resistant to reperfusion damage than low-passage cells, reperfusion damage was observed especially after hypoxia and acidosis with glucose and glutamine deprivation. Cell death induced by reperfusion after hypoxia with acidosis was not prevented by apoptosis, autophagy, or necroptosis inhibitors, but significantly decreased by ferrostatin-1, a ferroptosis inhibitor, and deferoxamine, an iron chelator. These data suggested that in our SIR model, cell death due to reperfusion injury is likely to occur via ferroptosis, which is related with ischemia/reperfusion-induced cell death in vivo. In conclusion, we established an optimal reperfusion injury model, in which ferroptotic cell death occurred by hypoxia and acidosis with or without glucose/glutamine deprivation under 10% dialyzed FBS.

• Food Science and Biotechnology
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• v.16 no.4
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• pp.632-635
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• 2007

This study examined the neuroprotective effect of scopoletin from Angelica dahurica against oxygen and glucose deprivation-induced neurotoxicity in a rat organotypic hippocampal slice culture. Scopoletin reduced the propidium iodide (PI) uptake, which is an indication of impaired cell membrane integrity. In addition, it inhibited the loss of NeuN, which represents the viability of neuronal cells. The results suggests that scopoletin from A. dahurica protects neuronal cells from the damage caused by oxygen and glucose deprivation.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.83-83
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• 2003

In our previous study, glucose deprivation was reported to induce the potentiated death and ATP loss in immunostimulated astroglia. And this vulnerability to glucose deprivation was due to overproduction of nitric oxide (NO) and hydrogen peroxide (H$_2$O$_2$). In the present study, the role of extracellular signal-regulated kinase 1/2 (ERK1/2) in the glucose deprivation-induced death of immunostimulated astroglia was examined. We showed that immunostimulation with LPS+IFN-ν activated the ERKl/2 signal pathway and produced a large amount of NO and H$_2$O$_2$. Generation of NO and H$_2$O$_2$ in immunostimulated astroglia was mediated via ERK1/2 signal pathways, since addition of the ERK kinase (MEKl) inhibitor PD98059 reduced NO and H$_2$O$_2$production. ERK1/2 activation-mediated NO and H$_2$O$_2$ production is due to an activation of iNOS and NADPH oxidase, respectively. Finally, we found that glucose deprivation caused ATP depletion and the augmented death in immunostimulated astroglia, which was also prevented by PD98059 treatment. These results demonstrate that the ERK1/2 signal pathways play an important role in glucose deprivation induced the death in immunostimulated astroglia by regulating the generation of NO and H$_2$O$_2$.

• Journal of Microbiology and Biotechnology
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• v.17 no.11
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• pp.1856-1861
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• 2007

Physiological cell conditions such as glucose deprivation and hypoxia play roles in the development of drug resistance in solid tumors. These tumor-specific conditions cause decreased expression of DNA topoisomerase $II{\alpha}$, rendering cells resistant to topo II target drugs such as etoposide. Thus, targeting tumor-specific conditions such as a low glucose environment may be a novel strategy in the development of anticancer drugs. On this basis, we established a novel screening program for anticancer agents with preferential cytotoxic activity in cancer cells under glucose-deprived conditions. We recently isolated an active compound, AA-98, from Streptomyces sp. AA030098 that can prevent stress-induced etoposide resistance in vitro. Furthermore, LC-MS and various NMR spectroscopic methods identified AA-98 as mithramycin, which belongs to the aureolic acid group of antitumor compounds. We found that mithramycin prevents the etoposide resistance that is induced by glucose deprivation. The etoposide-chemosensitive action of mithramycin was just dependent on strict low glucose conditions, and resulted in the selective cell death of etoposide-resistant HT-29 human colon cancer cells.