• 제목/요약/키워드: TorC1

검색결과 63건 처리시간 0.023초

Cytostatic in vitro Effects of DTCM-Glutarimide on Bladder Carcinoma Cells

  • Brassesco, Maria S.;Pezuk, Julia A.;Morales, Andressa G.;De Oliveira, Jaqueline C.;Valera, Elvis T.;Da Silva, Glenda N.;De Oliveira, Harley F.;Scrideli, Carlos A.;Umezawa, Kazuo;Tone, Luiz G.
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권5호
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    • pp.1957-1962
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    • 2012
  • Bladder cancer is a common malignancy worldwide. Despite the increased use of cisplatin-based combination therapy, the outcomes for patients with advanced disease remain poor. Recently, altered activation of the PI3K/Akt/mTOR pathway has been associated with reduced patient survival and advanced stage of bladder cancer, making its upstream or downstream components attractive targets for therapeutic intervention. In the present study, we showed that treatment with DTCM-glutaramide, a piperidine that targets PDK1, results in reduced proliferation, diminished cell migration and G1 arrest in 5637 and T24 bladder carcinoma cells. Conversely, no apoptosis, necrosis or autophagy were detected after treatment, suggesting that reduced cell numbers in vitro are a result of diminished proliferation rather than cell death. Furthermore previous exposure to 10 ${\mu}g/ml$ DTCM-glutarimide sensitized both cell lines to ionizing radiation. Although more studies are needed to corroborate our findings, our results indicate that PDK1 may be useful as a therapeutic target to prevent progression and abnormal tissue dissemination of urothelial carcinomas.

Pseudomonase sp. 960903에 의한 acetylcholinesterase 억제제의 생산 및 정제 (Production and Purification of Acetylcholinesterase Inhibitor from Pseudomonas sp960903)

  • 김경자
    • 한국미생물·생명공학회지
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    • 제28권6호
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    • pp.322-328
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    • 2000
  • To screen agent for the treat-ment of Alzhimers Disease several strains of bacteria producing acetylcholinesterase inhibitor ware isolated from soil. Strain 960903 showed strong acetylcholinesteras inhibitory activity and low butyrylcholinesterse inhibitory activity. The strain 960903 was identified as Pseudomonas sp. Acetylcholinesterase inhibitor ws highly achieved in fermentation medium containing soluble starch 3.0%, glycerol 1.0%, pharmamedia 0.5%, KCI 0.3%, $CaCO_3$ 0.2%, MgS $O_4$..$7H_2$O 0.05%, $KH_2$$PO_4$ 0.05%(pH6.5) at $30^{\circ}C$ for 4 days. Acetylcholinesterase inhibitor was purified by Diaion WA-30($OH^{-}$) column charomatography and cellulose column chromatography. Acetylcholinesterase inhibi-tor showd the maximum wavelength at 205 nm and was soluble in water, acetic acid, ethanol, methanol and dime-thyl sulfoxide. The concentration of 50% inhibition($IC_{50}$) of inhibitor against acetylcholinesterase was 25$\mu\textrm{g}$/ml. The inhibitor was inactivated on heating ar $100^{\circ}C$ fro 15 min and more stable in acidic region than alkaline region.n.

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Combinatorial Approach Using Caenorhabditis elegans and Mammalian Systems for Aging Research

  • Lee, Gee-Yoon;Sohn, Jooyeon;Lee, Seung-Jae V.
    • Molecules and Cells
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    • 제44권7호
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    • pp.425-432
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    • 2021
  • Aging is associated with functional and structural declines in organisms over time. Organisms as diverse as the nematode Caenorhabditis elegans and mammals share signaling pathways that regulate aging and lifespan. In this review, we discuss recent combinatorial approach to aging research employing C. elegans and mammalian systems that have contributed to our understanding of evolutionarily conserved aging-regulating pathways. The topics covered here include insulin/IGF-1, mechanistic target of rapamycin (mTOR), and sirtuin signaling pathways; dietary restriction; autophagy; mitochondria; and the nervous system. A combinatorial approach employing high-throughput, rapid C. elegans systems, and human model mammalian systems is likely to continue providing mechanistic insights into aging biology and will help develop therapeutics against age-associated disorders.

Ginsenoside Rh2 Induces Apoptosis via Activation of Caspase-1 and -3 and Up-Regulation of Bax in Human Neuroblastoma

  • Kim, Young-Soak;Jin, Sung-Ha
    • Archives of Pharmacal Research
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    • 제27권8호
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    • pp.834-839
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    • 2004
  • In human neuroblastoma SK-N-BE(2) cells undergoing apoptotic death induced by ginsenos-ide Rh2, a dammarane glycoside that was isolated from Panax ginseng C. A. Meyer, caspase-1 and caspase-3 were activated. The expression of Bax was increased in the cells treated with ginsenoside Rh2, whereas Bcl-2 expression was not altered. Treatment with caspase-1 inhibi-tor, Ac-YVAD-CMK, or caspase-3 inhibitor, Z-DEVD-FMK, partially inhibited ginsenoside Rh2-induced cell death but almost suppressed the cleavage of the 116 kDa PARP into a 85 kDa fragment. When the levels of p53 were examined in this process, p53 accumulated rapidly in the cells treated early with ginsenoside Rh2. These results suggest that activation of caspase-1 and -3 and the up-regulation of Bax are required in order for apoptotic death of SK-N-BE(2) cells to be induced by ginsenoside Rh2, and p53 plays an important role in the pathways to promote apoptosis.

최적의 상관 특성과 큰 선형 복잡도를 갖는 새로운 p-진 수열군 (New Family of p-ary Sequences with Optimal Correlation Property and Large Linear Span)

  • 장지용;김영식;노종선
    • 한국통신학회논문지
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    • 제28권9C호
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    • pp.835-842
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    • 2003
  • For an odd prime p and integer n, m and k such that n=(2m+1)ㆍk, a new family of p-ary sequences of period p$^{n}$ -1 with optimal correlation property is constructed using the p-ary Helleseth-Gong sequences with ideal autocorrelation, where the size of the sequence family is p$^{n}$ . That is, the maximum nontrivial correlation value R$_{max}$ of all pairs of distinct sequences in the family does not exceed p$^{n}$ 2/ +1, which means the optimal correlation property in terms of Welch's lower bound. It is also derived that the linear span of the sequences in the family is (m+2)ㆍn except for the m-sequence in the family.

Significance of $p27^{kip1}$ as potential biomarker for intracellular oxidative status

  • Quintos, Lesley;Lee, In-Ae;Kim, Hyo-Jung;Lim, Ji-Sun;Park, Ji-A;Sung, Mi-Kyung;Seo, Young-Rok;Kim, Jong-Sang
    • Nutrition Research and Practice
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    • 제4권5호
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    • pp.351-355
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    • 2010
  • Our previous proteomic study demonstrated that oxidative stress and antioxidant delphinidin regulated the cellular level of $p27^{kip1}$ (referred to as p27) as well as some heat shock proteins in human colon cancer HT 29 cells. Current study was conducted to validate and confirm the regulation of these proteins using both in vitro and in vivo systems. The level of p27 was decreased by hydrogen peroxide in a dose-dependent manner in human colon carcinoma HCT 116 (p53-positive) cells while it was increased upon exposure to hydrogen peroxide in HT 29 (p53-negative) cells. However, high concentration of hydrogen peroxide (100 ${\mu}M)$ downregulated p27 in both cell lines, but delphindin, one of antioxidative anthocyanins, enhanced the level of p27 suppressed by 100 ${\mu}M$ hydrogen peroxide. ICR mice were injected with varying concentrations of hydrogen peroxide, delphinidin and both. Western blot analysis for the mouse large intestinal tissue showed that the expression of p27 was upregulated by 25 mg/kg BW hydrogen peroxide. To investigate the association of p27 regulation with hypoxia-inducible factor 1-beta (HIF-$1{\beta}$), the level of p27 was analyzed in wild-type mouse hepatoma hepa1c1c7 and Aryl Hydrocarbon Nuclear Translocator (arnt, HIF-$1{\beta}$)-defective mutant BPRc1 cells in the absence and presence of hydrogen peroxide and delphinidin. While the level of p27 was responsive to hydrogen peroxide and delphinidin, it remained unchanged in BPRc1, suggesting that the regulation of p27 requires functional HIF-$1{\beta}$. We also found that hydrogen peroxide and delphinidin affected PI3K/Akt/mTOR signaling pathway which is one of upstream regulators of HIFs. In conclusion, hydrogen peroxide and antioxidant delphinidin seem to regulate intracellular level of p27 through regulating HIF-1 level which is, in turn, governed by its upstream regulators comprising of PI3K/Akt/mTOR signaling pathway. The results should also encourage further study for the potential of p27 as a biomarker for intracellular oxidative or antioxidant status.

Alginate-enclosed Microspheres를 이용한 메틸 프룩토시드의 연속생산공정 (Continuous Production Process of Methyl Fructoside Using Alginate-enclosed Microspheres)

  • 허주형;김해성
    • KSBB Journal
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    • 제10권2호
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    • pp.159-165
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    • 1995
  • 현탁상 효소반응기 (suspended bed enzyme reac­t tor)에서 alginate-enclosed microspheres를 이용 하여 에틸 프룩토시드의 연속생산과 그에 따른 반융 기 모사로부터 조업 조건의 최적화를 검토하고 메탈 프룩토시드의 연속생산 공정에 관한 체계적인 자료 를 제시하여 효소법에 의한 메틸 프룩토시드 연속생 산의 상엽적 실용성을 제고하고자 하였다. 그 결과, 자당농도 $20.291mol/\ell$, 반응온도 $25^{\circ}C$.에서 최척 에 탄올 함량은 30% (v/v), 최적 pH는 4.8, 최적 효소 활성도는 2U/ml로 나타났으며, 연속생산으로 얻을 수 있는 메틸 프룩토시드의 최대 농도는 $28.4g/\ell$이며, 에틸 프룩토시드의 생산성과 놓도를 함께 고려 한 최척 공간 속도는 $0.1hr^{-1}$부근으로 판단되었고, 그때의 생산성은 $2g/\ell-hr$이며, 그 수율은 47.1 %이 였다.

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Ginsenoside Rb1 and Rb2 upregulate Akt/mTOR signaling-mediated muscular hypertrophy and myoblast differentiation

  • Go, Ga-Yeon;Jo, Ayoung;Seo, Dong-Wan;Kim, Woo-Young;Kim, Yong Kee;So, Eui-Young;Chen, Qian;Kang, Jong-Sun;Bae, Gyu-Un;Lee, Sang-Jin
    • Journal of Ginseng Research
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    • 제44권3호
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    • pp.435-441
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    • 2020
  • Background: As a process of aging, skeletal muscle mass and function gradually decrease. It is reported that ginsenoside Rb1 and Rb2 play a role as AMP-activated protein kinase activator, resulting in regulating glucose homeostasis, and Rb1 reduces oxidative stress in aged skeletal muscles through activating the phosphatidylinositol 3-kinase/Akt/Nrf2 pathway. We examined the effects of Rb1 and Rb2 on differentiation of the muscle stem cells and myotube formation. Methods: C2C12 myoblasts treated with Rb1 and/or Rb2 were differentiated and induced to myotube formation, followed by immunoblotting for myogenic marker proteins, such as myosin heavy chain, MyoD, and myogenin, or immunostaining for myosin heavy chain or immunoprecipitation analysis for heterodimerization of MyoD/E-proteins. Results: Rb1 and Rb2 enhanced myoblast differentiation through accelerating MyoD/E-protein heterodimerization and increased myotube hypertrophy, accompanied by activation of Akt/mammalian target of rapamycin signaling. In addition, Rb1 and Rb2 induced the MyoD-mediated transdifferentiation of the rhabdomyosarcoma cells into myoblasts. Furthermore, co-treatment with Rb1 and Rb2 had synergistically enhanced myoblast differentiation through Akt activation. Conclusion: Rb1 and Rb2 upregulate myotube growth and myogenic differentiation through activating Akt/mammalian target of rapamycin signaling and inducing myogenic conversion of fibroblasts. Thus, our first finding indicates that Rb1 and Rb2 have strong potential as a helpful remedy to prevent and treat muscle atrophy, such as age-related muscular dystrophy.

THE HOMOLOGY REGARDING TO E-EXACT SEQUENCES

  • Ismael Akray;Amin Mahamad Zebari
    • 대한수학회논문집
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    • 제38권1호
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    • pp.21-38
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    • 2023
  • Let R be a commutative ring with identity. Let R be an integral domain and M a torsion-free R-module. We investigate the relation between the notion of e-exactness, recently introduced by Akray and Zebari [1], and generalized the concept of homology, and establish a relation between e-exact sequences and homology of modules. We modify some applications of e-exact sequences in homology and reprove some results of homology with e-exact sequences such as horseshoe lemma, long exact sequences, connecting homomorphisms and etc. Next, we generalize two special drived functor T or and Ext, and study some properties of them.

지질대사 조절에서 SREBP의 역할 (SREBP as a Global Regulator for Lipid Metabolism)

  • 이원화;서영교
    • 생명과학회지
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    • 제28권10호
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    • pp.1233-1243
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    • 2018
  • SREBPs는 지질의 항상성 및 대사를 조절하는 전사 인자이다. 이들은 내인성 콜레스테롤, 지방산(FA), 트리아실글리세롤(TG) 및 인지질 합성에 필요한 효소의 발현을 정밀하게 조절한다. 3종류의 SREBP 단백질은 2개의 다른 유전자에 의해 암호화 된다. SREBP1 유전자는 SREBP-1a와 SREBP-1c를 만든다. 이는 RNA의 alternative splicing에 의한 대체 프로모터의 이용으로부터 유도된다. SREBP-2는 별도의 유전자에서 유래한다. 또한, SREBPs는 ER 스트레스, 염증, 자가포식 및 세포사멸과 같은 수많은 병인과정에 관여하며, 비만, 이상 지질혈증, 당뇨병 및 비알콜성 지방간 질환 등을 유발하는 것으로 알려져 있다. 유전체의 분석은 SREBPs가 생물학적 신호 전달, 세포 신진 대사, 및 성장을 조절하는 중요한 연결고리임을 보여 주었다. 이 과정에서 SREBP는 PI3K-Akt-mTOR 경로를 통해 활성화 된다고 알려져 있다. 하지만 정확한 분자 메커니즘은 좀더 밝혀져야 한다. 이 리뷰에서는 세포, 기관 및 생물개체 수준의 생리학 및 병태 생리학 영역에서 SREBP의 역할에 대한 포괄적인 이해를 넓혀 줄 것이다.