• Food Science and Biotechnology
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• v.18 no.1
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• pp.234-238
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• 2009

Effects of ginseng on in vivo antioxidant capacities with age were studied in rats. All rats were reared in the conventional system. Ginseng-treated rats were supplied with ginseng water extracts (25 mg/kg/day) continuously from 6 weeks of age to spontaneous death. None of the rats showed any discernible adverse effects of treatment with ginseng-containing water. There was no significant difference in body weight (BW) gains with age between treated and control groups. However, ginseng extracts did cause a decrease in the level of serum low density lipoprotein (LDL)-cholesterol, glucose, and thiobarbituric acid reactive substances (TBARS) in the treated rats. The activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase in liver cytosol decreased with age in the control group. However, these enzyme activities were well maintained in the ginseng-treated rats and, especially, catalase and glutathione peroxidase activities were consistently higher than in control rats. The levels of total sulfhydryl group (T-SH) and glutathione reductase (GR) were unchanged, and glutathione-s-transferase (GST) activity gradually decreased with age in both groups. There were no differences in T-SH, GR, or GST between the control and treatment groups. These results indicate that long-term administration of ginseng retards age-related deterioration in some biochemical parameters such as cholesterol, glucose, and lactate dehydrogenase in serum and it has an enhancing effect on antioxidant capacity in the liver.

• Archives of Pharmacal Research
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• v.18 no.5
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• pp.301-307
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• 1995

In the particulate fraction obtained from PKC-down regulated K562 cells by treatment for 24 h with 200nM TPA, phosphorylation of two proteins with molecular weight, 100 kDa and 23 kDa (designated p100 and p23, respectvely) was depleted and addition of exogenous purified PKC to this fraction failed to testore their phosphorylation. However, in the soluble fraction, all of phosphoproteins abolished by long-term treatment with TPA were restored by exogenously added PKC. Phosphorylation of two proteins was increased by short-term tretment (20 min), and diminished with the persistant exposure to TPA as well as at a concentration as low as 1nM. When K562 cells were treated with 1 nM and 200 nM TPA for 24 h, phosphorylation of p100 was restored with or without exogenous PKC on 2-3day and 6day after removal of treated TPA, respectively. Two-dimensional electrophoresis of phosphoproteins revealed that phosphorylated p100 (pl=5.9) and p66 species were completely absent from the particulate fraction of K562 cells treated with 200nM TPA for 24 h. These results suggest that the interaction of sensitive endogenous substrates, p100 and p23 with the plasma membrane might be regulated by PKC-down regulation without displacement to the cytosol and the interaction of p100 with the membrane might be reveersible.

• Archives of Pharmacal Research
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• v.28 no.10
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• pp.1164-1169
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• 2005

Brain microglia are phagocytic cells that are the major inflammatory response cells of the central nervous system and widely held to play important pathophysiologic roles in Alzheimer's disease (AD) in both potentially neurotoxic responses and potentially beneficial phagocytic responses. In the study, we examined whether ginsonoside Rg3, a by-product of red ginseng, enhances the microglial phagocytosis of $A{\beta}$. We found that Rg3 promoted $A{\beta}$ uptake, internalization, and digestion. Increased maximal $A{\beta}$ uptake was observed at 4 and 8 h after Rg3 pretreatment (25 ${\mu}g/mL$), and the internalized $A{\beta}$ was almost completely digested from cells within 36 h when pretreated with Rg3 comparing with single non-Rg3-treated groups. The expression of MSRA (type A MSR) was also up-regulated by Rg3 treatment in a dose- and time-dependent manner which was coincidently identified in western blots for MSRA proteins in cytosol. These results indicate that microglial phagocytosis of $A{\beta}$ may be enhanced by Rg3 and the effect of Rg3 on promoting clearance of $A{\beta}$ may be related to the MSRA-associated action of Rg3. Thus, stimulation of the MSRA might contribute to the therapeutic potentials of Rg3 in microglial phagocytosis and digestion in the treatment of AD.

• Animal cells and systems
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• v.12 no.4
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• pp.211-217
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• 2008

Bax, a pro-apoptotic member of Bcl-2 family proteins, plays a central role in the mitochondria-dependent apoptosis. Apoptotic signals induce the translocation of Bax from cytosol into the mitochondria, which triggers the release of apoptogenic molecules such as cytochrome C and apoptosis-inducing factor, AIF. Bax-inhibiting peptide(BIP) is a cell permeable peptide comprised of five amino acids designed from the Bax-interaction domain of Ku70. Because BIP inhibits Bax translocation and Bax-mediated release of cytochrome C, BIP suppresses Bax-dependent apoptosis. In this study, we observed that BIP inhibited staurosporine-induced neuronal death in cultured cerebral cortex and cerebellar granule cells, but BIP failed to rescue granule cells from trophic signal deprivation-induced neuronal death, although both staurosporine-induced and trophic signal deprivation-induced neuronal death are dependent on Bax. These findings suggest that the mechanisms of the Bax activation may differ depending on the type of cell death induction, and thus BIP exhibits selective suppression of a subtype of Bax-dependent neuronal death.

• Molecules and Cells
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• v.38 no.4
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• pp.312-317
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• 2015

Depletion of intracellular zinc by N,N,N,N-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) induces p53-mediated protein synthesis-dependent apoptosis of mouse cortical neurons. Here, we examined the requirement for poly(ADP-ribose) polymerase (PARP)-1 as an upstream regulator of p53 in zinc depletion-induced neuronal apoptosis. First, we found that chemical inhibition or genetic deletion of PARP-1 markedly attenuated TPEN-induced apoptosis of cultured mouse cortical neurons. Poly(ADP-ribosyl)ation of p53 occurred starting 1 h after TPEN treatment. Suggesting the critical role of PARP-1, the TPEN-induced increase of stability and activity of p53 as well as poly(ADP-ribosyl)ation of p53 was almost completely blocked by PARP inhibition. Consistent with this, the induction of downstream pro-apoptotic proteins PUMA and NOXA was noticeably reduced by chemical inhibitors or genetic deletion of PARP-1. TPEN-induced cytochrome C release into the cytosol and caspase-3 activation were also blocked by inhibition of PARP-1. Taken together, these findings indicate that PARP-1 is essential for TPEN-induced neuronal apoptosis.

• Molecules and Cells
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• v.43 no.8
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• pp.705-717
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• 2020

While the growth factors like insulin initiate a signaling cascade to induce conformational changes in the mechanistic target of rapamycin complex 1 (mTORC1), amino acids cause the complex to localize to the site of activation, the lysosome. The precise mechanism of how mTORC1 moves in and out of the lysosome is yet to be elucidated in detail. Here we report that microtubules and the motor protein KIF11 are required for the proper dissociation of mTORC1 from the lysosome upon amino acid scarcity. When microtubules are disrupted or KIF11 is knocked down, we observe that mTORC1 localizes to the lysosome even in the amino acid-starved situation where it should be dispersed in the cytosol, causing an elevated mTORC1 activity. Moreover, in the mechanistic perspective, we discover that mTORC1 interacts with KIF11 on the motor domain of KIF11, enabling the complex to move out of the lysosome along microtubules. Our results suggest not only a novel way of the regulation regarding amino acid availability for mTORC1, but also a new role of KIF11 and microtubules in mTOR signaling.

• Korean Journal of Microbiology
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• v.30 no.5
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• pp.333-338
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• 1992

Saccharomyces cerevisiae contains 10-nm tilament ring which lies just under the inner surface of the plasma membrane within the mother-bud neck. Although H)-nm filaments may he involved in cellular morphogenesis. their role and organization are not clear. Here we report the production of antihodies specific for the CDel2 protein hy use of gene fusion techniques. and studies on the organization and function of IO-nm filaments using these antibodies. The CDCl2 protein arc translated through the whtlle cell cycle and present in the cytosol. 'They are polymerized just before bud emergence and unpolymerized alier cytokinesis. and do not have organizational relationship with actin. Thc possible role of 10-nm filaments is the determination of bud emergence site and completion of cytokinesis.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.36 no.6
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• pp.573-577
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• 2003

Effects of 4-nonylphenol (4-NP) on mixed function oxygenase (MFO) in the kidneies of rockfish (Sebastes schlegeli) were investigated. The cytochrome P45O (CYP) contents and NADPH cytochrome P450 reductase, NADH cytochrome b5 reductase and 7-ethoxyredorufin-O-deethylase (EROD) activities of microsome, glutathione S-transferase (GST) activity of cytosol in rockfish exposed to 4-NP for 7 days using an intraperitoneal injection (25 mg/kg) were quantitatively determined. The GST activity of rockfish exposed to 4-NP were higher, up to 5.2 times higher, than those in the control fish. The activities of NADPH-and NADH-dependent reductases were inhibited. On the other hand, CYP contents and EROD activity of the 4-NP exposed fish demonstrated neither an increasing or decreasing trend.

• Bulletin of the Korean Chemical Society
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• v.26 no.8
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• pp.1225-1228
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• 2005

C-terminal fragments of APP (APP-CTs), that contain A$\beta$ sequence, are found in neurotic plaques, neurofibrillary tangles and the cytosol of lymphoblastoid cells obtained from AD patients. CT26, Thr639-Asp664 (TVIVITLVMLKKKQYTSIHH GVVEVD) includes not only the transmembrane domain but also the cytoplasmic domain of APP. This sequence is produced from cleavage of APP by caspase and $\gamma$-secretase. In this study, the solution structure of CT26 was investigated using NMR spectroscopy and circular dichroism (CD) spectropolarimeter in various membrane-mimicking environments. According to CD spectra and the tertiary structure of CT26 determined in TFE-containing aqueous solution, CT26 has an α-helical structure from $Val^{2}\;to\;Lys^{11}$ in TFE-containing aqueous solution. However, according to CD data, CT26 adopts a $\beta$-sheet structure in the SDS micelles and DPC micelles. This result implies that CT26 may have a conformational transition between $\alpha$-helix and $\beta$-sheet structure. This study may provide an insight into the conformational basis of the pathological activity of the C-terminal fragments of APP in the model membrane.

• BMB Reports
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• v.33 no.6
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• pp.448-453
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• 2000

In yeast the key gluconeogenic enzyme, fructose-1,6-bisphosphatase (FBPase), is selectively targeted from the cytosol to the lysosome (vacuole) for degradation when glucose starved cells are replenished with glucose. The pathway for glucose induced FBPase degradation is unknown. To identify the receptor-mediated degradation pathway of FBPase, we investigated the presence of the FBPase receptor on the vacuolar membrane by cell fractionation experiments and binding assay using vid mutant (vacuolar import and degradation), which is defective in the glucose-induced degradation of FBPase. FBPase sedimented in the pellets from vid24-1 mutant after centrifugation at $15,000{\times}g$ for 15 min, suggesting that FBPase is associated with subcellular structures. Cell fractionation experiments revealed that FBPase is preferentially associated with the vacuole, but not with other organelles in vid24-1. FBPase enriched fractions that cofractionated with the vacuole were sensitive to proteinase K digestion, indicating that FBPase is peripherally associated with the vacuole. We developed an assay for the binding of FBPase to the vacuole. The assay revealed that FBPase bound to the vacuole with a Kd of $2.3{\times}10^6M$. The binding was saturable and specific. These results suggest that a receptor for FBPase degradation exists on the vacuolar membrane. It implies the existence of the receptor-mediated degradation pathway of FBPase by the lysosome.