• Title/Summary/Keyword: Translational control

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β-Lapachone-Induced Apoptosis is Associated with Inhibition of Cyclooxygenase-2 Activity in Human Lung Cancer A549 Cells (β-lapachone에 의한 A549 인체폐암세포의 apoptosis 유도와 cyclooxygenase-2 활성 저하)

  • Choi, Yung-Hyun
    • Journal of Life Science
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    • v.21 no.10
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    • pp.1494-1499
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    • 2011
  • ${\beta}$-lapachone, a quinone of lapachol extracted from the bark of the lapacho tree, has been found to induce apoptosis in various human cancer cells. In the present study, we investigated further possible mechanisms by which ${\beta}$-lapachone exerts its pro-apoptotic action in cultured human lung cancer A549 cells. ${\beta}$-lapachone treatment resulted in inhibition of growth and induction of apoptosis in a concentration-dependent manner, as determined by MTT assay and flow cytometry analysis. The induction of apoptosis by ${\beta}$-lapachone was associated with up-regulation of the expression of p53 and p21 in both transcriptional and translational levels, and the phosphorylation of p53. In addition, ${\beta}$-lapachone activated caspase-3 and -9, and induced degradation of caspase-3 target proteins such as poly (ADP-ribose) polymerase (PARP) and ${\beta}$-catenin. Furthermore, ${\beta}$-lapachone treatment caused a progressive decrease in the expression levels of cyclooxygenase (COX)-2 without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin E2 synthesis. Taken together, these results indicated that ${\beta}$-lapachone may have therapeutic potential in human lung cancer treatment.

Floral Pigmentation and Expression of Anthocyanin-Related Genes in Bicolored Roses 'Pinky Girl' as Affected by Temporal Heat Stress (일시적 고온 스트레스가 복색 장미 'Pinky Girl'의 화색 및 관련 유전자 발현에 미치는 영향)

  • Lee, Seul Ki;Kim, Wan Soon
    • Horticultural Science & Technology
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    • v.33 no.6
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    • pp.923-931
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    • 2015
  • This study was conducted to investigate petal pigmentation and the expression patterns of anthocyanin-related genes in bicolored roses 'Pinky Girl' treated with temporal heat stress (THS). Cyanin accumulation in petals was correlated with floral bud development and started rapidly as floral buds began to open, defined as the $4^{th}$ stage of floral bud development ($S_4$). This stage seems to be most susceptible to petal pigmentation. The total of cyanin pigmentation at blooming was significantly decreased (by 45.5%) with exposure to THS ($39/18^{\circ}C$ for three days at $S_4$) in comparison with control. Meanwhile, the expression of anthocyanin-related genes such as CHS, CHI, F3'H, DFR, ANS, 3GT, and 5GT was relatively promoted by THS. Only F3H was less expressed (by 26.7%) with THS treatment; thus, F3H could be a key gene for bicolor promotion in 'Pinky Girl' among anthocyanin-related genes. Overall, the expression pattern of the most anthocyanin-related genes did not match the trends of cyanin pigmentation in petals. These results suggest that floral pigmentation could be associated with other mechanisms related to anthocyanin biosynthesis such as post-translational effects and regulatory genes.

Oocyte Maturation Process of Zebrafish (Danio rerio), an Emerging Animal Model (새로운 실험 동물 모델인 제브라피쉬(Danio rerio)의 난자 성숙 기작)

  • Han, Seung Jin
    • Journal of Life Science
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    • v.25 no.10
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    • pp.1184-1195
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    • 2015
  • The zebrafish is an emerging vertebrate model organism in reproductive biology. The oocyte maturation of zebrafish is triggered by maturation inducing hormone (MIH, 17α,20β-Dihydroxy-4-pregnen-3-one). In almost all animals, the oocyte maturation is governed by activation of pre-MPF which consists of cyclinB and inactive Cdk1. In the oocyte of Xenopus and mice, the activity of Cdk1 is regulated in two ways, one is the interaction with cyclinB and the other is phosphorylation/dephosphorylation of T14/Y15 residues on the Cdk1 by Wee1 and Cdc25. Unlike Xenopus and mice that have a sufficient amount of pre-MPF, pre-MPF is absent in GV oocyte of most teleost including zebrafish. Therefore, the activation of MPF during zebrafish oocyte maturation might totally depend on de novo synthesis of cyclinB proteins. It is reported that the translation of maternal mRNA is regulated by combination of several RNA binding proteins such as CPEB, Dazl, Pum1/Pum2, and insulin-like growth factor2 mRNA-binding protein 3 in the zebrafish oocytes. However, the definitive mechanism of these proteins to regulate the translation of stored maternal mRNAs remains to be elucidated. Therefore, the investigation of the maturation process of the zebrafish oocyte will provide new information that can help identify the role of translational control in early vertebrate oocyte maturation.

Anti-proliferative Effects of Water Extract of Agaricus blazei Murill in Human Lung Cancer Cell Line A549 (A549 인체폐암세포의 증식에 미치는 신령버섯 추출물의 영향에 관한 연구)

  • Choi, Woo-Young;Park, Cheol;Lee, Jae-Yun;Kim, Gi-Young;Park, Yeong-Min;Jeong, Yong-Kee;Lee, Won-Ho;Choi, Yung-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.33 no.8
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    • pp.1237-1245
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    • 2004
  • Agaricus blazei Murill is a medicinal mushroom native to Brazil. It used to be a source of antitumor and immunoactive compounds and considered a health food in many countries. In the present study, it was examined the effects of water extract of A. blazei (WEAB) on the growth of human lung carcinoma cell line A549 in order to investigate the anti-proliferative mechanism by WEAB. Treatment of A549 cells to WEAB resulted in the growth inhibition, morphological change and induction of apoptotic cell death in a dose-dependent manner as measured by MTT assay and flow cytometric analysis. Flow cytometric analysis revealed that WEAB caused G2/M phase arrest of the cell cycle, which was associated with a down-regulation of cyclin A in both transcriptional and translational levels. WEAB treatment induced a marked up-regulation of cyclin-dependent kinase (Cdk) inhibitor p21, however, the levels of Cdk2, Cdc2, Wee1, Cdc25C and p53 expression were remained unchanged in WEAB treated cells. In addition, WEAB treatment inhibited the levels of cyclooxygenase (COX)-2 mRNA and protein without alteration of COX-l expression. Taken together, these findings suggest that WEAB may be a potential chemotherapeutic agent for the control of human lung carcinorma cells and further studies will be needed to identify the active compounds that confer the anti-cancer activity of WEAB. Once such compounds are identified, the mechanisms by which they exert their effects can begin to be characterized.

The Stimulatory Effect of Garnoderma lucidum and Phellinus linteus on the Antioxidant Enzyme Catalase

  • Park, Jin-Seu;Lee, Byung-Ryong;Jin, Li Hua;Kim, Choong-Kwon;Choi, Kyung-Soon;Bahn, Jae-Hoon;Lee, Kil-Soo;Kwon, Hyeok-Yil;Chang, Hyun-Woo;Baek, Nam-In;Lee, Hwang-Eunjoo;Kang, Jung-Hoon;Cho, Sung-Woo;Choi, Soo-Young
    • BMB Reports
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    • v.34 no.2
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    • pp.144-149
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    • 2001
  • Antioxidant enzymes, scavengers of the reactive oxygen intermediate (ROI), are involved in numerous defense systems in cells. In the present study, we investigated the effects of the hot-water extracts of two medicinally potent mushrooms (Ganoderma lucidum and Phellinus linteus) on the activity and expression of antioxidant enzymes in vitro and in vivo. The mushroom extracts stimulated the catalase activity in a dose-dependent manner in vitro, whereas the other antioxidant enzymes (such as superoxide dismutase (SOD), glutathione peroxidase (GPx)) were unaffected by the extracts. The catalytic activity of catalase in the liver and brain was significantly increased after the oral treatment of the mushroom extracts (2.5 g/kg) to ICR mice for 2 months. Western blot analysis of the liver and brain tissues revealed that the expression level of catalase in the mice, treated with both mushroom extracts, was significantly increased compared to that of the control mice. However, the level of the SOD expression in the mice treated with the natural product extracts was unchanged under the same experimental conditions. Although the mechanisms for the stimulatory effect of the catalase expression by these extracts remains unclear, these results suggest that the ingredients of the Ganoderma lucidum and Phellinus linteus extracts act as an activator of catalase, and regulate the expression of catalase at the translational or transcriptional level.

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Dose-Dependent Associations between Wine Drinking and Breast Cancer Risk - Meta-Analysis Findings

  • Chen, Jia-Yan;Zhu, Hong-Cheng;Guo, Qing;Shu, Zheng;Bao, Xu-Hui;Sun, Feng;Qin, Qin;Yang, Xi;Zhang, Chi;Cheng, Hong-Yan;Sun, Xin-Chen
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1221-1233
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    • 2016
  • Purpose: To investigate any potential association between wine and breast cancer risk. Materials and Methods: We quantitatively assessed associations by conducting a meta-analysis based on evidence from observational studies. In May 2014, we performed electronic searches in PubMed, EmBase and the Cochrane Library to identify studies examining the effect of wine drinking on breast cancer incidence. The relative risk (RR) or odds ratio (OR) were used to measure any such association. Results: The analysis was further stratified by confounding factors that could influence the results. A total of twenty-six studies (eight case-control and eighteen cohort studies) involving 21,149 cases were included in our meta-analysis. Our study demonstrated that wine drinking was associated with breast cancer risk. A 36% increase in breast cancer risk was observed across overall studies based on the highest versus lowest model, with a combined RR of 1.0059 (95%CI 0.97-1.05) in dose-response analysis. However, 5 g/d ethanol from wine seemed to have protective value from our non-linear model. Conclusions: Our findings indicate that wine drinking is associated with breast cancer risk in a dose-dependent manner. High consumption of wine contributes to breast cancer risk with protection exerted by low doses. Further investigations are needed for clarification.

Autocrine Regulation of Gonadotropin-releasing Hormone (GnRH) Operates at Multiple Control levels of GnRH Gene Expression in GT1-1 Neuronal Cells

  • Jin Han;Sehyung Cho;Woong Sun;Kyungjin Kim
    • Animal cells and systems
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    • v.2 no.4
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    • pp.483-488
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    • 1998
  • We previously found that a potent gonadotropin-releasing hormone (GnRH) agonist, buserelin, decreases GnRH promoter activity together with GnRH mRNA level, providing evidence for an autoregulatory mechanism operating at the level of GnRH gene transcription in immortalized GT1-1 neuronal cells. To examine whether agonist-induced decrease in GnRH mRNA level requires the continuous presence of buserelin, we performed a pulse-chase experiment of buserelin treatment. Short-term exposure (15 min) of GT1-1 neuronal cells to buserelin ($10{\mu}M$) was able to decrease GnRH mRNA levels when determined 24 h later. When GT1-1 cells were treated with buserelin ( $10{\mu}M$) for 30 min and then incubated for 1, 3, 6, 12, 24, and 48 h after buserelin removal, a significant decrease in GnRH mRNA levels was observed after the 12 h incubation period. These data indicate that inhibitory signaling upon buserelin treatment may occur rapidly, but requires a long time (at least 12 h) to significantly decrease the GnRH mRNA level. To examine the possible involvement of de novo synthesis and/or mRNA stability in buserelin-induced decrease in GnRH gene expression, actinomycin D ($5{\mu}m/ml$), a potent RNA synthesis blocker, was co-treated with buserelin. Actinomycin D alone failed to alter basal GnRH mRNA Revel, but blocked the buserelin-induced decrease in GnRH mRNA level at 12 h of post-treatment. These data suggest that buserelin may exert its inhibitory action by altering the stability of GnRH mRNA. Moreover, a polvsomal RNA separation by sucrose gradient centrifugation demonstrated that buserelin decreased the translational efficiency of the transcribed GnRH mRNA. Taken together, these results clearly indicate that GnRH agonist buserelin acts as an inhibitory signal at multiple levels such as transcription mRNA stability, and translation.

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Piceatannol-Induced G1 Arrest of the Cell Cycle is Associated with Inhibition of Prostaglandin E2 Production in Human Gastric Cancer AGS Cells (Piceatannol에 의한 AGS 인체 위암세포의 G1 Arrest 및 Prostaglandin E2 생성의 억제)

  • Choi, Yung-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.7
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    • pp.907-913
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    • 2012
  • Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene) is a polyphenol detected in grapes, rhubarb, and sugarcane. Although recent experimental data revealed that this compound is known to exhibit immunosuppressive and antitumorigenic activities in several cell lines, the molecular mechanisms underlying anticancer activity are poorly understood. In the present study, we investigated possible further mechanisms by which piceatannol exerts its anti-proliferative action in cultured human gastric cancer AGS cells. Piceatannol treatment resulted in the inhibition of growth and G1 arrest of the cell cycle in a concentration-dependent manner, as determined by MTT assay and flow cytometry analysis. The induction of G1 arrest by piceatannol was associated with the modulation of cyclin-dependent kinases (Cdks) and cyclins, up-regulation of the expression of Cdk inhibitor p21 (WAF1/CIP1) in both transcriptional and translational levels, and the inhibition of phosphorylation of retinoblastoma proteins and E2F1 expression. In addition, piceatannol treatment caused a progressive decrease in the expression levels of cyclooxygenase (COX)-2 without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin $E_2$ synthesis.

Ball Velocity Changes Depending on the Different Linear Momentum of Putter Head during the Putting Strokes (퍼팅 스트로크에서 퍼터의 선 운동량 크기에 따른 볼의 이동 속도 변화에 관한 연구)

  • Park, Jin
    • Korean Journal of Applied Biomechanics
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    • v.17 no.4
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    • pp.83-88
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    • 2007
  • The purpose of this study was to investigate the ball velocity changes depending on the different linear momentum of putter head. For this study, two different moving conditions(25cm free fall and 35cm free fall) of putter head were set. And two different types of ground conditions were used which are artificial grass green($180cm{\times}600cm{\times}1cm$) and glass green($40cm{\times}130cm{\times}1cm$). Movements of putter head and ball were recorded with 2 HD video cameras(60 Hz, 1/500s shutter speed). Small size control object($18.5cm{\times}18.5cm{\times}78.5cm$) was used in this study. Ball and putter head velocities were calculated by the First Central Difference Method(Hamill & Knutzen, 1995). Linear momentum of ball and putter head were calculated with mass and its velocities. Before impact, the velocity of the putter head of 35cm free fall was about 30% greater than that of the putter head of 25cm free fall. Linear momentum of putter head of 35cm free fall was about 0.355-0.364kg m/s and 25cm free fall was 0.251 kg m/s. After impact, putter head lost its linear momentum about 14-19% and adjusting time of putter head after impact would be 0.1 second. After 0.1 second, putter moved the route same as before impact. Maximum ball velocities were appeared 0.08s-0.10s after impact no matter what the ground conditions are. Ball velocities struck by 35cm free fall were 30 % faster than 25cm free fall. Linear momentum of ball struck by putter head was greater than that of expected amount because the moving ball has translational energy and rotational energy. Future study must treat three things. One is ball must struck by the different putters with different materials. Another is two-piece ball and three-piece ball should be used for the same condition studies. The other is height of center of rotation of club should be changed. In this study, the height of center of rotation of club head is 71cm from the ground. But recently many golfers used the long putter. Therefore next study should apply the different height of center of rotation of club head.

Identification of Potential Substrates of N-acteylglucosamine Kinase by a Proteomic Approach (프로테오믹스를 이용한 N-아세틸글루코사민 인산화효소 기질단백질의 동정)

  • Lee, HyunSook;Moon, Il Soo
    • Journal of Life Science
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    • v.23 no.4
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    • pp.586-594
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    • 2013
  • Post-translational O-GlcNAc modification (O-GlcNAcylation) of serine or threonine is a new protein modulation mechanism. In contrast to the classical glycosylation, O-GlcNAcylation occurs in a one-step transfer of O-GlcNAc on both nuclear and cytoplasmic proteins. In contrast to the general consensus that O-GlcNAc is a final modification, a recent paper (J Proteome Res. 2011 10:2725-2733) showed the presence of O-GlcNAc-P on a synaptic assembly protein AP180. This finding raises a fundamental question about its prevalence. To address this question, we used proteomics to identify those proteins that were phospho-signal enriched by GlcNAc kinase (NAGK). Comparison of pDsRed2-$NAGK_{WT}$-transfected HEK293T cell extract with pDsRed2-$NAGK_{D107A}$-transfected control culture revealed 15 phospho-signal increased spots. Excluding those spots that had no detectable amount of protein expression yielded 7 spots, which were selected for ID determination. Among these, two duplicate spots (two $HSP90{\beta}$ and two ENO1 spots) were shown to be O-GlcNAcylated, two (dUTP nucleotidohydrolase mitochondrial isoform 2, glutathione S-transferase P) were not known to be involved in O-GlcNAcylation, and one (heat shock protein gp96 precursor or grp94) was a glycoprotein. The increase in the phospho-levels of O-GlcNAc by NAGK strongly indicates that these proteins are phosphorylated on O-GlcNAc. Our present data support the idea that O-GlcNAc is not a terminal modification.