• The Korean Journal of Physiology and Pharmacology
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• 제15권3호
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• pp.149-156
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• 2011

Golgi SNAP receptor complex 1 (GS28) has been implicated in vesicular transport between intra-Golgi networks and between endoplasmic reticulum (ER) and Golgi. Additional role(s) of GS28 within cells have not been well characterized. We observed decreased expression of GS28 in rat ischemic hippocampus. In this study, we examined the role of GS28 and its molecular mechanisms in neuronal (SK-N-SH) cell death induced by hydrogen peroxide ($H_2O_2$). GS28 siRNA-transfected cells treated with $H_2O_2$ showed a significant increase in cytotoxicity under glutathione (GSH)-depleted conditions after pretreatment with buthionine sulfoximine, which corresponded to an increase of intracellular reactive oxygen species (ROS) in the cells. Pretreatment of GS28 siRNA-transfected cells with p38 chemical inhibitor significantly inhibited cytotoxicity; we also observed that p38 was activated in the cells by immunoblot analysis. We confirmed the role of p38 MAPK in cotransfected cells with GS28 siRNA and p38 siRNA in the cell viability assay, flow cytometry, and immunoblot. Involvement of apoptotic or autophagic processes in the cells was not shown in the cell viability, flow cytometry, and immunoblot analyses. However, pretreatment of the cells with necrostatin-1 completely inhibited $H_2O_2$-induced cytotoxicity, ROS generation, and p38 activation, indicating that the cell death is necroptotic. Collectively these data imply that $H_2O_2$ induces necroptotic cell death in the GS28 siRNA-transfected cells and that the necroptotic signals are mediated by sequential activations in RIP1/p38/ROS. Taken together, these results indicate that GS28 has a protective role in $H_2O_2$-induced necroptosis via inhibition of p38 MAPK in GSH-depleted neuronal cells.

• Journal of Ginseng Research
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• 제37권3호
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• pp.315-323
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• 2013

Ginseng is known to have antistress effects. Previously, red ginseng (RG) was shown to repress stress-induced peptidyl arginine deiminase type IV (PADI4) via estrogen receptor ${\beta}$ ($ER{\beta}$) in the brain, thus inhibiting brain cell apoptosis. Moreover, tumor necrosis factor (TNF)-${\alpha}$ plays a critical role in immobilization (IMO) stress. However, the signaling pathway of RG-mediated repressesion of inflammation is not completely understood. In this study, we determined how RG modulated gene expression in stressed brain cells. Since secretion of TNF-${\alpha}$ is modulated via TNF-${\alpha}$ converting enzyme (TACE) and nuclear factor (NF)-${\kappa}B$, we examined the inflammatory pathway in stressed brain cells. Immunohistochemistry revealed that TACE was induced by IMO stress, but RG repressed TACE induction. Moreover, PADI4 siRNA repressed TACE expression compared to the mock transfected control suggesting that PADI4 was required for TACE expression. A reporter assay also revealed that $H_2O_2$ oxidative stress induced NF-${\kappa}B$ in neuroblastoma SK-N-SH cells, however, RG pretreatment repressed NF-${\kappa}B$ induction. These findings were supported by significant induction of nitric oxide and reactive oxygen species (ROS) by oxidative stress, which could be repressed by RG administration. Taken together, RG appeared to repress stress-induced PADI4 via TACE and NF-${\kappa}B$ in brain cells thus preventing production of ROS and subsequently protecting brain cells from apoptosis.

• Biomolecules & Therapeutics
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• 제12권3호
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• pp.189-193
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• 2004

Over the past several years, research efforts have been directed both at economically producing valuable substances from the wood biomass and at producing lignolytic enzymes at a lower cost. In the present study, we found that Phellinus igniarius, the basidiomycetes, secreted lignin peroxidase as a main lignolytic enzyme, which was detected maximum activity at 16th day of culture and showed 37 kDa of molecular mass in identification by activity assay and purification by anion-exchange chromatography. The Phellinus igniarius-derived lignin peroxidase hydrolyzed steam-exploded wood (Quercus mongolica) powder into small molecules showing cytotoxicity against cancer cel1s (HepG2 hepatoma, SK-N-SH neuroblastoma, B16 melanoma, MBT-2 bladder cancer). In addition, the enzyme hydrlysates of lignins (ELg) that were extracted from the steam-exploded oak showed more potent cytotoxic effects on the cancer cells than the enzyme hydrolysates of wood biomass (EWp), indicating that the cytotoxic effect of EWp may be due to the enzyme-degraded products of lignin among the lignocellulosics. Furthermore, the cytotoxic effect of ELg on Chang, normal liver cells, was much less potent than that of ELg on HepG2 and B16 cancer cells, indicating that the cytotoxic effect of ELg may be specific for cancer cells. The present results suggest that Phellinus igniarius may be a useful resource for the large-scale production of lignin peroxidase and that the lignin peroxidase may be applied for the generation of valuable biodegradation products from wood lignocellulosics for medical use.