• Title/Summary/Keyword: anti-apoptosis

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Neuroprotective effects of resveratrol on 6-hydroxydopamine-induced damage of SH-SY5Y cell line (6-Hydroxydopamine 유발 SH-SY5Y 세포주 손상에 대한 resveratrol의 신경보호 효과)

  • Chang, Geon-Cheon;Kim, Hyoung-Chun;Wie, Myung-Bok
    • Korean Journal of Veterinary Research
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    • v.54 no.1
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    • pp.1-6
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    • 2014
  • Parkinson's disease is known to exhibit progressive degeneration of the dopaminergic neurons in the substantia nigra via inhibition of glutathione metabolism. It is well known that 6-Hydroxydopamine (6-OHDA) induces Parkinson's disease-like symptoms, while resveratrol (3,5,4'-trihydroxystilbene) has been shown to have anti-inflammatory and antioxidant effects. In the present study, we investigated the neuroprotective effects of resveratrol, a phytoalexin found in grapes and various plants, on 6-OHDA-induced cell damage to the SH-SY5Y human neuroblastoma cell line. Resveratrol (5 and 10 ${\mu}M$) inhibited 6-OHDA (60 ${\mu}M$)-induced cytotoxicity in SH-SY5Y cells and induced a reduction of the number of apoptotic nuclei caused by 6-OHDA treatment. Additionally, the total apoptotic rate of cells treated with both resveratrol (10 ${\mu}M$) and 6-OHDA (60 ${\mu}M$) was less than that of 6-OHDA treated cells. Resveratrol also dose-dependently (1, 5 and 10 ${\mu}M$) scavenged reactive oxygen species (ROS) induced by 6-OHDA in SH-SY5Y cells and prevented depletion of glutathione in response to the 6-OHDA-induced cytotoxicity in the glutathione assay. Overall, these results indicate that resveratrol exerts a neuroprotective effect against 6-OHDA-induced cytotoxicity of SH-SY5Y cells by scavenging ROS and preserving glutathione.

The Review on the Study of Bee Venom in the Journals of Korean Medicine (국내 봉독 관련 연구에 대한 고찰)

  • Han, Chang-Hyun;Lee, Yong-Seok;Kwon, Oh-Min;Lee, Young-Joon
    • Korean Journal of Acupuncture
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    • v.30 no.1
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    • pp.27-36
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    • 2013
  • Objectives : The focus of the analysis was laid on changes in research pertaining to bee venom in regards to time progression. Methods : We collected 365 articles on Bee venom study result from OASIS system using the Keyword 'bee venom, apitoxin, apitherapy, bee sting'. We figured out number and percentage of theses according to year, study method, journal, subject. Results : Bee venom papers published in the journal of korean medicine from 1976. The classification of papers associated with bee venom, clinical studies outnumbered the other study types by a ratio of 1.3 to 1, followed by 138 for experimental papers, and 22 for literature studies. Proportion of Experimental Papers Classified According to the Theme, 16 for pain-killing, 14 papers concentrated on apoptosis anticancer, 13 for anti inflammatory, 11 for arthritis, and other disorders were followed. Type analysis of papers associated with bee venom in clinical trials, lumbar disorders comprised 38 out of 205 papers, 35 papers concentrated on upper limb disorders, 34 papers concentrated on systemic disease, followed by the effect on body. Conclusions : Bee venom is a treatment method based on the unique theory of Korean traditional medicine. Its effort and academical approach on bee venom are expected to receive positive evaluation through numerous research works.

Microarray Analysis of Alteration in Gene Expression by Acori graminei rhizoma (AGR) Water-Extract in a Hypoxic Model of Cultured Rat Cortical Cells (흰쥐 대뇌세포의 저산소증 모델에서 석창포(石菖浦 Acori graminei rhizoma. AGR)에 의한 유전자 표현 변화의 microarray 분석)

  • Park, Dong-Jun;Jung, Seung-Hyun;Moon, Il-Soo;Lee, Won-Chol;Shin, Gil-Jo
    • Journal of Life Science
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    • v.17 no.1 s.81
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    • pp.150-161
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    • 2007
  • Acori graminei Rhizomn (AGR) is a perennial herb which has been used clinically as a traditional oriental medicine against stroke, Alzheimer's disease, and vascular dementia. We investigated the effect of AGR on the modulation of gene expression profile in a hypoxic model of cultured rat cortical cells. Rat cerebrocortical cells were grown in Neurobasal medium. On DIV12, cells were treated with AGR $(10ug/m\ell)$, given a hypoxic shock (2% $O_2$, 3 hr) on DIV14, and total RNAs were prepared one day after shock. Microarray analyses indicated that the expression levels of most genes were altered within the global M values +0.5 and -0.5, i.e., 40% increase or decrease. There were 750 genes which were upregulated by < global M +0,2, while 700 genes were downregulated by > global M -0.2. The overall profile of gene expression suggests that AGR suppresses apoptosis (upregulation of anti-apopotic genes such as TEGT, TIEG, Dad, p53, and downregulation of pro-apopotic genes such as DAPK, caspase 2, pdcd8), ROS (upregulation of RARa, AhR), and that AGR has neurotrophic effects (upregulation of Aktl, Akt2). These results provide a platform for investigation of the molecular mechanism of the effect of AGR in neuroprotection.

Expression Profiling of Lipopolysaccharide Target Genes in RAW264.7 Cells by Oligonucleotide Microarray Analyses

  • Huang, Hao;Park, Cheol-Kyu;Ryu, Ji-Yoon;Chang, Eun-Ju;Lee, Young-Kyun;Kang, Sam-Sik;Kim, Hong-Hee
    • Archives of Pharmacal Research
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    • v.29 no.10
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    • pp.890-897
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    • 2006
  • In inflammatory responses, induction of cytokines and other immune regulator genes in macrophages by pathogen-associated signal such as lipopolysaccharide (LPS) plays a crucial role. In this study, the gene expression profile changes by LPS treatment in the macrophage/monocyte lineage cell line RAW264.7 was investigated. A 60-mer oligonucleotide microarray of which probes target 32381 mouse genes was used. A reverse transcription-in vitro translation labeling protocol and a chemileuminescence detection system were employed. The mRNA expression levels in RAW264.7 cells treated for 6 h with LPS and the control vehicle were compared. 747 genes were up-regulated and 523 genes were down-regulated by more than 2 folds. 320 genes showing more than 4-fold change by LPS treatment were further classified for the biological process, molecular function, and signaling pathway. The biological process categories that showed high number of increased genes include the immunity and defense, the nucleic acid metabolism, the protein metabolism and modification, and the signal transduction process. The chemokine-cytokine signaling, interleukin signaling, Toll receptor signaling, and apoptosis signaling pathways involved high number of genes differentially expressed in response to LPS. These expression profile data provide more comprehensive information on LPS-target genes in RAW264.7 cells, which will be useful in comparing gene expression changes induced by extracts and compounds from anti-inflammatory medicinal herbs.

Pyruvate Protection against Endothelial Cytotoxicity Induced by Blockade of Glucose Uptake

  • Chung, Se-Jin;Lee, Se-Hee;Lee, Yong-Jin;Park, Hyoung-Sook;Bunger, Rolf;Kang, Young-Hee
    • BMB Reports
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    • v.37 no.2
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    • pp.239-245
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    • 2004
  • We have previously demonstrated that the redox reactant pyruvate prevents apoptosis in the oxidant model of bovine pulmonary artery endothelial cells (BPAEC), and that the anti-apoptotic mechanism of pyruvate is mediated in part via the mitochondrial matrix compartment. However, cytosolic mechanisms for the cytoprotective feature of pyruvate remain to be elucidated. This study investigated the pyruvate protection against endothelial cytotoxicity when the glycolysis inhibitor 2-deoxy-D-glucose (2DG) was applied to BPAEC. Millimolar 2DG blocked the cellular glucose uptake in a concentration- and time-dependent manner with >85% inhibition at $\geq$5 mM within 24 h. The addition of 2DG evoked BPAEC cytotoxicity with a substantial increase in lipid peroxidation and a marked decrease in intracellular total glutathione. Exogenous pyruvate partially prevented the 2DG-induced cell damage with increasing viability of BPAEC by 25-30%, and the total glutathione was also modestly increased. In contrast, 10 mM L-lactate, as a cytosolic reductant, had no effect on the cytotoxicity and lipid peroxidation that are evoked by 2DG. These results suggest that 2DG toxicity may be a consequence of the diminished potential of glutathione antioxidant, which was partially restored by exogenous pyruvate but not L-lactate. Therefore, pyruvate qualifies as a cytoprotective agent for strategies that attenuate the metabolic dysfunction of the endothelium, and cellular glucose oxidation is required for the functioning of the cytosolic glutathione/NADPH redox system.

Transduced Tat-CIAPIN1 reduces the inflammatory response on LPS- and TPA-induced damages

  • Yeo, Hyeon Ji;Shin, Min Jea;You, Ji Ho;Kim, Jeong Su;Kim, Min Young;Kim, Dae Won;Kim, Duk-Soo;Eum, Won Sik;Choi, Soo Young
    • BMB Reports
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    • v.52 no.12
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    • pp.695-699
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    • 2019
  • Cytokine-induced apoptosis inhibitor 1 (CIAPIN1), known as an anti-apoptotic and signal-transduction protein, plays a pivotal role in a variety of biological processes. However, the role of CIAPIN1 in inflammation is unclear. We investigated the protective effects of CIAPIN1 in lipopolysaccharide (LPS)-exposed Raw 264.7 cells and against inflammatory damage induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in a mouse model using cell-permeable Tat-CIAPIN1. Transduced Tat-CIAPIN1 significantly reduced ROS production and DNA fragmentation in LPS-exposed Raw 264.7 cells. Also, Tat-CIAPIN1 inhibited MAPKs and NF-κB activation, reduced the expression of Bax, and cleaved caspase-3, COX-2, iNOS, IL-6, and TNF-α in LPS-exposed cells. In a TPA-induced animal model, transduced Tat-CIAPIN1 drastically decreased inflammation damage and inhibited COX-2, iNOS, IL-6, and TNF-α expression. Therefore, these findings suggest that Tat-CIAPIN1 might lead to a new strategy for the treatment of inflammatory skin disorders.

The Protective Effects of Acupuncture on Oxidative Stress Caused by Cadmium in the Kidney (카드뮴으로 유발된 산화적 스트레스에 대한 침 자극의 신장 보호 효과)

  • Shin, Hwa Young;Lee, Hyun Jong;Kim, Jae Soo
    • Journal of Acupuncture Research
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    • v.32 no.1
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    • pp.1-11
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    • 2015
  • Objectives : This study was performed to inquire into the protective effects of acupuncture on oxidative stress caused by cadmium accumulation in the kidney. Methods : Sprague-Dawley male($150{\pm}30g$) rats were stabilized for 1 week and divided into 5 groups: normal, control, $LR_3$ acupuncture, $BL_{23}$ acupuncture and sham acupuncture. For three days experimental groups received oral doses of cadmium 2 mg/kg twice a day. Acupuncture was applied bilaterally at each point 10 times for two weeks. The depth of stimulation was 1 mm at right angles and torsion of acupuncture was produced 2 times per second for 1 minute. The kidneys were extracted and weighed after two weeks, and renal function was confirmed through blood urea nitrogen(BUN). We measured reactive oxygen species of the serum and kidney, and compared expression levels of superoxide dismutase(SOD), catalase, glutathione peroxidase(Gpx), nuclear factor erythroid derived 2-related factor 2(Nrf-2), heme oxygenase-1(HO-1), nuclear factor-${\kappa}B$(NF-${\kappa}B)$, cyclooxygenase-2(COX-2), inducible nitric oxide synthase (iNOS), Bax and Cytochrome c. Results : The $LR_3$ acupuncture group and $BL_{23}$ acupuncture group experienced significantly increased kidney weight, and decreased BUN compared to control group. In terms of oxidative stress, the $LR_3$ acupuncture group and $BL_{23}$ acupuncture group experienced significantly reduced reactive oxygen species compared to the control group. Conclusions : The $LR_3$ acupuncture group and $BL_{23}$ acupuncture group experienced showed the effects of antioxidant, anti-inflammatory and apoptosis protection. The $BL_{23}$ acupuncture group was more effective than $LR_3$ acupuncture group.

Protective Effect of Korean Red Ginseng against Aflatoxin B1-Induced Hepatotoxicity in Rat

  • Kim, Yong-Seong;Kim, Yong-Hoon;Noh, Jung-Ran;Cho, Eun-Sang;Park, Jong-Ho;Son, Hwa-Young
    • Journal of Ginseng Research
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    • v.35 no.2
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    • pp.243-249
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    • 2011
  • Korean red ginseng (KRG), the steamed root of Panax ginseng Meyer, has a variety of biological properties, including anti-inflammatory, antioxidant and anticancer effects. Aflatoxin $B_1$ ($AFB_1$) produced by the Aspergillus spp. causes acute hepatotoxicity by lipid peroxidation and oxidative DNA damage, and induces liver carcinoma in humans and laboratory animals. This study was performed to examine the protective effects of KRG against hepatotoxicity induced by $AFB_1$ using liver-specific serum marker analysis, histopathology, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. In addition, to elucidate the possible mechanism of hepatoprotective effects, superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde were analyzed. Rats were treated with 250 mg/kg of KRG (KRG group) or saline ($AFB_1$ group) for 4 weeks and then received 150 ${\mu}g/kg$ of $AFB_1$ intraperitoneally for 3 days. Rats were sacrificed at 12 h, 24 h, 48 h, 72 h, or 1 wk after $AFB_1$ treatment. In the KRG pre-treatment group, serum alanine aminotransferase, aspartate aminotransferase, and malondialdehyde levels were low, but superoxide dismutase, catalase, and glutathione peroxidase activities were high as compared to the $AFB_1$ alone group. Histopathologically, $AFB_1$ treatment induced necrosis and apoptosis in hepatocytes, and led to inflammatory cells infiltration in the liver. KRG pre-treatment ameliorated these changes. These results indicate that KRG may have protective effects against hepatotoxicity induced by $AFB_1$ that involve the antioxidant properties of KRG.

Induction of Differentiation of the Cultured Rat Mammary Epithelial Cells by Triterpene Acids

  • Paik, Kee-Joo;Jeon, Seong-Sill;Chung, Hae-Young;Lee, Kyung-Hee;Kim, Kyu-Won;Chung, Joon-Ki;Kim, Nam-Deuk
    • Archives of Pharmacal Research
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    • v.21 no.4
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    • pp.398-405
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    • 1998
  • We investigated the effects of triterpene acids (TAs), ursolic acid (UA) and oleanolic acid (OA), on the induction of proliferation and differentiation of normal rat mammary epithelial cells (RMEC) or organoids cultured in Matrigel or primary culture system. To elucidate the effects, we tested their differentiation inducing activities with intercellular communication ability, cell cycle patterns, induction of apoptosis, and morphological differentiation in the three dimensional extracellular culture system. To study the changes of RMEC subpopulation in culture, the cultured cells were isolated, immunostained with peanut lectin (PNA) and anti-Thy-1.1 antibody and then analyzed with flow cytometry. Four different subpopulations, such as PNA and Thy-1.1 negative cells (B-), PNA positive cells (PNA+), Thy-1.1 positive cells (Thy-1.1+), PNA and Thy-1.1 positive cells (B+), were obtained and the size of each subpopulation was changed in culture with time in the presence of TAs. Intercellular communication was observed in culture for 7 days in TAs-treated cells, but not in culture for 4 days with scrape-loading dye transfer technique. $G_2$/M phase cells and the number of apoptotic population were increased in TAs-treated groups in cell cycle analyses. S phase fractions were reduced and the change of $G_1$ phase cells was not observed. The colonies with distinct multicelfular structures, such as stellate, ductal, webbed, squamous, lobulo-ductal colonies, were observed in Matrigel culture and the frequencies of each colony were changed in the presence of TAs. These results suggest that UA and OA have differentiation inducing effects on rat mammary epithelial cells in primary or in Matrigel culture.

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LINC00703 Acts as a Tumor Suppressor via Regulating miR-181a/KLF6 Axis in Gastric Cancer

  • Yang, Haiyang;Peng, Minqi;Li, Yanjiao;Zhu, Renjie;Li, Xiang;Qian, Zhengjiang
    • Journal of Gastric Cancer
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    • v.19 no.4
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    • pp.460-472
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    • 2019
  • Purpose: Long noncoding RNA 00703 (LINC00703) was found originating from a region downstream of Kruppel-like factor 6 (KLF6) gene, having 2 binding sites for miR-181a. Since KLF6 has been reported as a target of miR-181a in gastric cancer (GC), this study aims to investigate whether LINC00703 regulates the miR-181a/KLF6 axis and plays a functional role in GC pathogenesis. Materials and Methods: GC tissues, cell lines, and nude mice were included in this study. RNA binding protein immunoprecipitation (RIP) and pull-down assays were used to evaluate interaction between LINC00703 and miR-181a. Quantitative real-time polymerase chain reaction and western blot were applied for analysis of gene expression at the transcriptional and protein levels. A nude xenograft mouse model was used to determine LINC00703 function in vivo. Results: We revealed that LINC00703 competitively interacts with miR-181a to regulate KLF6. Overexpression of LINC00703 inhibited cell proliferation, migration/invasion, but promoted apoptosis in vitro, and arrested tumor growth in vivo. LINC00703 expression was found to be decreased in GC tissues, which was positively correlated with KLF6, but negatively with the miR-181a levels. Conclusions: LINC00703 may have an anti-cancer function via modulation of the miR-181a/KLF6 axis. This study also provides a new potential diagnostic marker and therapeutic target for GC treatment.