• Molecules and Cells
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• v.37 no.9
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• pp.672-684
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• 2014

The exact causes of cell death in Parkinson's disease (PD) remain unknown despite extensive studies on PD.The identification of signaling and metabolic pathways involved in PD might provide insight into the molecular mechanisms underlying PD. The neurotoxin 1-methyl-4-phenylpyridinium ($MPP^+$) induces cellular changes characteristic of PD, and $MPP^+$-based models have been extensively used for PD studies. In this study, pathways that were significantly perturbed in $MPP^+$-treated human neuroblastoma SH-EP cells were identified from genome-wide gene expression data for five time points (1.5, 3, 9, 12, and 24 h) after treatment. The mitogen-activated protein kinase (MAPK) signaling pathway and endoplasmic reticulum (ER) protein processing pathway showed significant perturbation at all time points. Perturbation of each of these pathways resulted in the common outcome of upregulation of DNA-damage-inducible transcript 3 (DDIT3). Genes involved in ER protein processing pathway included ubiquitin ligase complex genes and ER-associated degradation (ERAD)-related genes. Additionally, overexpression of DDIT3 might induce oxidative stress via glutathione depletion as a result of overexpression of CHAC1. This study suggests that upregulation of DDIT3 caused by perturbation of the MAPK signaling pathway and ER protein processing pathway might play a key role in $MPP^+$-induced neuronal cell death. Moreover, the toxicity signal of $MPP^+$ resulting from mitochondrial dysfunction through inhibition of complex I of the electron transport chain might feed back to the mitochondria via ER stress. This positive feedback could contribute to amplification of the death signal induced by $MPP^+$.

• Journal of Applied Biological Chemistry
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• v.63 no.2
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• pp.137-145
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• 2020

Oxidative stress is one of the pathogenic mechanisms of various neurodegenerative diseases, such as Alzheimer's disease. Neuroglia, the most abundant cells in the brain, is thought to play an important role in the antioxidant defense system and neuronal metabolic support against neurotoxicity and oxidative stress. We investigated the protective effect of paeoniflorin (PF) against oxidative stress in C6 glial cells. Exposure of C6 glial cells to hydrogen peroxide (H₂O₂, 500 μM) significantly decreased cell viability and increased amounts of lactate dehydrogenase (LDH) release, indicating H₂O₂-induced cellular damage. However, treatment with PF significantly attenuated H₂O₂-induced cell death as shown by increased cell survival and decreased LDH release. The H₂O₂-stimulated reactive oxygen species production was also suppressed, and it may be associated with improvement of superoxide dismutase activity by treatment with PF. In addition, an increase in ratio of Bcl-2/Bax protein expression was observed after treatment with PF. In particular, the down-stream of the apoptotic signaling pathway was inhibited in the presence of PF, mostly by reduction of cleaved-poly ADP ribose polymerase, cleaved caspase-3, and -9 protein expression. Furthermore, H₂O₂-induced phosphorylation of c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2 was attenuated by treatment with PF. Taken together, neuroprotective effect of PF against oxidative stress probably result from the regulation of apoptotic pathway in C6 glial cells. In conclusion, our findings suggest that PF may be a potent therapeutic agent for neurodegenerative disorders.

• Korean Journal of Pharmacognosy
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• v.42 no.2
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• pp.201-208
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• 2011

Obesity occur from the imbalance between energy intake and energy expenditure. Obesity is a complex chronic disease that is suggested to cause other metabolic disorders such as type 2 diabetes, hyperlipidemia, hypertension, and arteriosclerosis. In this study, our purpose is to investigate the anti-hyperglycemic and anti-obesitic effects of Maydis stigma water extract in 3T3-L1 adipocytes and db/db mice. Maydis stigma water extract at dose of 100 and 500 ${\mu}g/ml$ slowly inhibited cell viability as compared to that of control in mature adipocytes. Also, the additions of 50 and 250 ${\mu}g/ml$ of Maydis stigma water extract significantly inhibited the lipid accumulations and CCAAT/enhancer-binding protein(C/EBP) ${\alpha}$ and peroxisome proliferator-activated receptor(PPAR) ${\gamma}$ expressions with dose-dependent manner in 3T3-L1 adipocytes. Maydis stigma water extract at 250, 500, and 1000 ${\mu}g/ml$ only showed the increasing pattern on lipolysis activity. The oral treatment of Maydis stigma water extract (100 or 400 mg/kg body weight) in db/db mice only showed tendency to decrease body weight, food efficiency ratio (FER), HbA1c, blood glucose, total cholesterol, triglyceride, and the adipocyte size of in db/db mice. However, Maydis stigma water extract increased the insulin level in a dose dependent manner. Thus these results indicate that Maydis stigma water extracxt inhibits adipogenesis through regulation of C/EBP${\alpha}$ and PPAR${\gamma}$ expressions in 3T3-L1 adipocytes and shows anti-hyperglycemic effect through increase of insulin secretion in db/db mice.

• Toxicological Research
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• v.6 no.2
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• pp.167-182
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• 1990

Dietary restriction (caloric restriction) is the only intervention which has been reliably shown to extend the maximum life span of warm-blooded animals and delay the many phenomena associated with aging. It is also one of the most effective modulators of toxicity, especially cancer endpoints. In spite of the known modulator effects of caloric restriction, the biological mechanisms responsible for these effects had not been in vestigated until recently. The National Center for Toxicological Research (NCTR), in a collaborative effort with the National Institute of Aging (NIA), initiated a project whereby nine (9) combinations of rodent species/strains and diets were fed both restricted and ad libitum. The NIA's initiative was to identify biomarkers of aging whereas NCTR's initiative was to identify the biological effects associated with the profound effects caloric restriction has in protecting against both spontaneous (age-related) and chemically-induced toxic endpoints. Independent of sex or species, caloric restriction has similar effects on body temperature, oxygen consumption and $CO_2$production. Caloric restriction also decreased lipid glycolysis and metabolism in rats and mice, which suggest decreased production of metabolites which could lead to fatty acid epoxide formation. The age-associated loss of ciradian regulation of intermediate enzymes is also significantly reduced. Moreover, caloric restriction reduced the age-associated feminization of sexually dimorphic liver isozymes, increased several glucocorticoid responsive isozymes, elevated glucagon/insulin ratios, produced less microsomal superoxide and enhanced the capacity for utilzing detoxicating metabolic pathways. Calorically restricted rats have less than half the number of aflatoxin ($AFB_1$)-DNA adducts than ad libitum animals and urinary excretion of $AFB_1$ was increased significantly. Finally, DNA repair mechanisms are enhanced and oncogene expression is decreased in calorically restricted animals.

• Biomolecules & Therapeutics
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• v.16 no.4
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• pp.431-436
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• 2008

To identify genes whose expression correlated with biological features of therapy-related AML (t-AML), we analyzed the expression profiles of de novo AML t(9;11) and t-AML t(9;11) bone marrow samples using previously published SAGE data. Three-hundred twenty-nine transcripts that satisfied statistical (P<0.05) and magnitude-of-change ($\geq$ 4-fold) criteria were identified as differentially expressed between de novo AML t(9;11) and t-AML t(9;11) cells. Of these transcripts, 301 (91%) matched known genes or ESTs and were classified according to functional categories (http://david.abcc.ncifcrf.gov/). The majority of differentially expressed genes in t-AML t(9;11) were involved in the regulation of biological and metabolic processes. Especially prominent among these were genes related to immune and drug responses. These results establish a framework for developing new drugs for the treatment of t-AML.

• Horticultural Science & Technology
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• v.32 no.5
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• pp.684-693
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• 2014

Abiotic stress conditions such as cold, drought, and salinity trigger physiological and morphological changes and yield loss in plants. Hence, plants adapt to adverse environments by developing tolerance through complex regulation of genes related to various metabolic processes. This study was conducted to construct a coexpression network for multidirectional analysis of salt-stress response genes in Brassica rapa (Chinese cabbage). To construct the coexpression network, we collected KBGP-24K microarray data from the B. rapa EST and microarray database (BrEMD) and performed time-based expression analyses of B. rapa plants. The constructed coexpression network model showed 1,853 nodes, 5,740 edges, and 142 connected components (correlation coefficient > 0.85). On the basis of the significantly expressed genes in the network, we concluded that the development of salt tolerance is closely related to the activation of $Na^+$ transport by reactive oxygen species signaling and the accumulation of proline in Chinese cabbage.

• The Journal of Korean Medicine
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• v.36 no.1
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• pp.75-85
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• 2015

Objectives: Type 2 diabetes mellitus is a metabolic disease characterized by insulin resistance and high blood glucose level from progressive insulin secretory defect. The rhizome of Atractylodes japonica Koidz. (AJ) has been used for treatment of retention of water in oriental medicine. The aim of this study is to examine the effects of AJ on type 2 diabetes rats. Methods: Type 2 diabetes was induced by 60% high fat diet and low dose streptozotocin. Rats were divided into 4 groups (n = 6); Nor (normal control group), Con (diabetic group treated with vehicle), Met (diabetic group treated with 200 mg/kg metformin) and AJ (diabetic group treated with 100 mg/kg AJ). The body weights and food intakes were measured during the treatment period. After 4 weeks treatment, blood glucose level, HOMA-IR, and protein expressions of IRS-1, p-IRS-1, PPAR-${\gamma}$, and GLUT4 were measured, and histopathological examination of beta cell was performed. Results: Compared with the control group, blood glucose level and HOMA-IR were reduced in rats treated with AJ. Impaired beta cells in pancreas of rats were recovered and phosphorylation of IRS-1 was increased in rats treated with AJ. And also, protein expressions of PPAR-${\gamma}$ and GLUT4 were increased by treatment of AJ. Conclusions: The results suggest that Atractylodes japonica Koidz. may have anti-diabetic effect on type 2 diabetic rats through regulation of blood glucose level and insulin resistance. Therefore Atractylodes japonica Koidz. may have positive effects on patients with type 2 diabetes.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.1
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• pp.59-68
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• 1999

Chemically induced hypoxia has been shown to induce a depletion of ATP. Since intracellular free $Mg^{2+}\;([Mg^{2+}]_i)$ appears to be tightly regulated following cellular energy depletion, we hypothesized that the increase in $[Mg^{2+}]_i$ would result in $Mg^{2+}$ extrusion following hormonal stimulation. To determine the relation between $Mg^{2+}$ efflux and cellular energy state in a hypoxic rat heart and isolated myocytes, $[Mg^{2+}]_i,$ ATP and $Mg^{2+}$ content were measured by using mag-fura-2, luciferin-luciferase and atomic absorbance spectrophotometry. $Mg^{2+}$ effluxes were stimulated by norepinephrine (NE) or cAMP analogues, respectively. $Mg^{2+}$ effluxes induced by NE or cAMP were more stimulated in the presence of metabolic inhibitors (MI). Chemical hypoxia with NaCN (2 mM) caused a rapid decrease of cellular ATP within 1 min. Measurement of $[Mg^{2+}]_i$ confirmed that ATP depletion was accompanied by an increase in $[Mg^{2+}]_i.$ No change in $Mg^{2+}$ efflux was observed when cells were incubated with MI. In the presence of MI, the cAMP-induced $Mg^{2+}$ effluxes were inhibited by quinidine, imipramine, and removal of extracellular $Na^+.$ In addition, after several min of perfusion with $Na^+-free$ buffer, a large increase in $Mg^{2+}$ efflux occurred when $Na^+-free$ buffer was switched to 120 mM $Na^+$ containing buffer. A similar $Mg^{2+}$ efflux was observed in myocytes. These effluxes were inhibited by quinidine and imipramine. These results indicate that the activation of $Mg^{2+}$ effluxes by hormonal stimulation is directly dependent on intracellular $Mg^{2+}$ contents and that these $Mg^{2+}$ effluxes appear to occur through the $Na^+-dependent\;Na^+/Mg^{2+}$ exchange system during chemical hypoxia.

• Journal of Microbiology and Biotechnology
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• v.18 no.11
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• pp.1747-1754
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• 2008

Acidithiobaeillus ferrooxidans ATCC 23270 is an important model organism for bioleaching and bioremediation studies owing to its diverse metabolic capabilities, whereas lix984n is a widely used extractant. Little is known about the response of cbb genes in A. ferrooxidans to lix984n shock. Thus, to elucidate the response of the $CO_2$ fixation genes in A. ferrooxidans ATCC 23270 to the addition of lix984n, the gene expression of cbb genes was examined using a real-time PCR. Although a natural increase or decrease in the expression of most cbb genes was observed after 5 min of shock with 3% (v/v) lix984n, sdhC and cbbR exhibited quick responses to the shock. Ten min of shock had a greater effect on the cbb gene expression, yet 15 min of shock had a significant effect on the Calvin cycle in A. ferrooxidans ATCC 23270, as the expression of all the cbb genes reached a very high level. Therefore, after a short lix984n shock, a solution of A. ferrooxidans can be re-used for bioleaching.

• Journal of Ginseng Research
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• v.40 no.1
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• pp.9-17
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• 2016

Background: Alzheimer's disease (AD) is a progressive brain disease, for which there is no effective drug therapy at present. Ginsenoside Rg1 (G-Rg1) and G-Rg2 have been reported to alleviate memory deterioration. However, the mechanism of their anti-AD effect has not yet been clearly elucidated. Methods: Ultra performance liquid chromatography tandem MS (UPLC/MS)-based metabolomics was used to identify metabolites that are differentially expressed in the brains of AD mice with or without ginsenoside treatment. The cognitive function of mice and pathological changes in the brain were also assessed using the Morris water maze (MWM) and immunohistochemistry, respectively. Results: The impaired cognitive function and increased hippocampal $A{\beta}$ deposition in AD mice were ameliorated by G-Rg1 and G-Rg2. In addition, a total of 11 potential biomarkers that are associated with the metabolism of lysophosphatidylcholines (LPCs), hypoxanthine, and sphingolipids were identified in the brains of AD mice and their levels were partly restored after treatment with G-Rg1 and G-Rg2. G-Rg1 and G-Rg2 treatment influenced the levels of hypoxanthine, dihydrosphingosine, hexadecasphinganine, LPC C 16:0, and LPC C 18:0 in AD mice. Additionally, G-Rg1 treatment also influenced the levels of phytosphingosine, LPC C 13:0, LPC C 15:0, LPC C 18:1, and LPC C 18:3 in AD mice. Conclusion: These results indicate that the improvements in cognitive function and morphological changes produced by G-Rg1 and G-Rg2 treatment are caused by regulation of related brain metabolic pathways. This will extend our understanding of the mechanisms involved in the effects of G-Rg1 and G-Rg2 on AD.