• 제목/요약/키워드: protein resistance

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장기간의 지구성 운동 또는 저항성 운동이 중년 흰쥐의 골격근 내 단백질 동화 및 이화기전에 미치는 영향 (The effects of long term endurance or resistance exercise training on anabolic and catabolic pathway in skeletal muscle of middle-aged rats)

  • 정수련;김기진;고진호
    • 한국체육학회지인문사회과학편
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    • 제55권6호
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    • pp.691-700
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    • 2016
  • 본 연구의 목적은 장기간의 지구성 운동 또는 저항성 운동이 중년 흰쥐의 골격근 내 단백질 합성과 분해에 미치는 영향을 규명하는 것이다. 50 주령의 male Wistar rat 30 마리를 이용하여 3집단(좌업, 지구성 운동집단, 저항성 운동집단)으로 무선배정한 후 12 주간 처치를 실시하였다. 연구결과 12주간의 저항성운동은 중년 쥐의 족저근 내 Akt/mTOR 신호전달체계를 활성화시켰고, FoxO1/MuRF1 단백질 발현을 저해하였다. 지구성 운동은 mTOR 신호전달체계에는 영향을 미치지 않았으나 FoxO1/MuRF1 단백질 발현을 저해하였고, AMPK/PGC-1α 발현을 증가시켰다. 요약하면 12주간의 운동트레이닝은 중년 흰쥐의 골격근 내 단백질 동화/이화반응에 긍정적인 영향을 미쳤으며, 지구성 운동은 근단백질 이화반응의 저해를 통해서 노화근육의 단백질 균형에 영향을 미치는 것으로 나타났다. 이러한 결과를 통해서 근 손실에 따른 근 기능의 저하가 가시화되기 시작하는 중년을 대상으로 실시되는 운동처방 시 근 감소증 예방 및 치료를 위해 저항성 운동만이 아니라 중강도 이상의 지구성 운동도 유효할 것으로 생각된다.

Overexpression of cysteine protease in transgenic Brassica rapa enhances resistance to bacterial soft rot and up-regulate the expression of various stress-regulated genes

  • Jung, Yu-Jin;Kang, Kwon-Kyoo
    • Journal of Plant Biotechnology
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    • 제37권3호
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    • pp.327-336
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    • 2010
  • Cysteine proteases have been known as a critical factor in plant defense mechanisms in pineapple, papaya, or wild fig. Papain or ficin is one kind of cysteine proteases that shows toxic effects to herbivorous insects and pathogenic bacteria. However, resistance to bacterial soft rot of plants genetically engineered with cysteine protease has been little examined thus far. We cloned a cysteine protease cDNA from Ananas comosus and introduced the gene into Chinese cabbage (Brassica rapa) under the control of the cauliflower mosaic virus 35S promoter. The transgene was stably integrated and actively transcribed in transgenic plants. In comparisons with wild-type plants, the $T_2$ and $T_3$ transgenic plants exhibited a significant increase in endo-protease activity in leaves and enhanced resistance to bacterial soft rot. A cDNA microarray analysis revealed that several genes were more abundantly transcribed in the transgenic than in the wild type. These genes encode a glyoxal oxidase, PR-1 protein, PDF1, protein kinase, LTP protein, UBA protein and protease inhibitor. These results suggest an important role for cysteine protease as a signaling regulator in biotic stress signaling pathways, leading to the build-up of defense mechanism to pathogenic bacteria in plants.

Phosphorylation of rpS3 by Lyn increases translation of Multi-Drug Resistance (MDR1) gene

  • Woo Sung Ahn;Hag Dong Kim;Tae Sung Kim;Myoung Jin Kwak;Yong Jun Park;Joon Kim
    • BMB Reports
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    • 제56권5호
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    • pp.302-307
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    • 2023
  • Lyn, a tyrosine kinase that is activated by double-stranded DNA-damaging agents, is involved in various signaling pathways, such as proliferation, apoptosis, and DNA repair. Ribosomal protein S3 (RpS3) is involved in protein biosynthesis as a component of the ribosome complex and possesses endonuclease activity to repair damaged DNA. Herein, we demonstrated that rpS3 and Lyn interact with each other, and the phosphorylation of rpS3 by Lyn, causing ribosome heterogeneity, upregulates the translation of p-glycoprotein, which is a gene product of multidrug resistance gene 1. In addition, we found that two different regions of the rpS3 protein are associated with the SH1 and SH3 domains of Lyn. An in vitro immunocomplex kinase assay indicated that the rpS3 protein acts as a substrate for Lyn, which phosphorylates the Y167 residue of rpS3. Furthermore, by adding various kinase inhibitors, we confirmed that the phosphorylation status of rpS3 was regulated by both Lyn and doxorubicin, and the phosphorylation of rpS3 by Lyn increased drug resistance in cells by upregulating p-glycoprotein translation.

A small molecule approach to degrade RAS with EGFR repression is a potential therapy for KRAS mutation-driven colorectal cancer resistance to cetuximab

  • Lee, Sang-Kyu;Cho, Yong-Hee;Cha, Pu-Hyeon;Yoon, Jeong-Soo;Ro, Eun Ji;Jeong, Woo-Jeong;Park, Jieun;Kim, Hyuntae;Kim, Tae Il;Min, Do Sik;Han, Gyoonhee;Choi, Kang-Yell
    • Experimental and Molecular Medicine
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    • 제50권11호
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    • pp.12.1-12.12
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    • 2018
  • Drugs targeting the epidermal growth factor receptor (EGFR), such as cetuximab and panitumumab, have been prescribed for metastatic colorectal cancer (CRC), but patients harboring KRAS mutations are insensitive to them and do not have an alternative drug to overcome the problem. The levels of ${\beta}$-catenin, EGFR, and RAS, especially mutant KRAS, are increased in CRC patient tissues due to mutations of adenomatous polyposis coli (APC), which occur in 90% of human CRCs. The increases in these proteins by APC loss synergistically promote tumorigenesis. Therefore, we tested KYA1797K, a recently identified small molecule that degrades both ${\beta}$-catenin and Ras via $GSK3{\beta}$ activation, and its capability to suppress the cetuximab resistance of KRAS-mutated CRC cells. KYA1797K suppressed the growth of tumor xenografts induced by CRC cells as well as tumor organoids derived from CRC patients having both APC and KRAS mutations. Lowering the levels of both ${\beta}$-catenin and RAS as well as EGFR via targeting the $Wnt/{\beta}$-catenin pathway is a therapeutic strategy for controlling CRC and other types of cancer with aberrantly activated the $Wnt/{\beta}$-catenin and EGFR-RAS pathways, including those with resistance to EGFR-targeting drugs attributed to KRAS mutations.

Molecular Basis of Drug Resistance: Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and Anaplastic Lymphoma Kinase Inhibitors

  • Yang, Sei-Hoon
    • Tuberculosis and Respiratory Diseases
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    • 제75권5호
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    • pp.188-198
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    • 2013
  • Over the past decade, several kinase inhibitors have been approved based on their clinical benefit in cancer patients. Unfortunately, in many cases, patients develop resistance to these agents via secondary mutations and alternative mechanisms. To date, several major mechanisms of acquired resistance, such as secondary mutation of the epidermal growth factor receptor (EGFR) gene, amplification of the MET gene and overexpression of hepatocyte growth factor, have been reported. This review describes the recent findings on the mechanisms of primary and acquired resistance to EGFR tyrosine kinase inhibitors and acquired resistance to anaplastic lymphoma kinase inhibitors, primarily focusing on non-small cell lung carcinoma.

Modulation of Drug Resistance in Ovarian Cancer Cells by Inhibition of Protein Kinase C-alpha (PKC-α) with Small Interference RNA (siRNA) Agents

  • Zhao, Li-Jun;Xu, Heng;Qu, Jun-Wei;Zhao, Wan-Zhou;Zhao, Yi-Bing;Wang, Jin-Hua
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권8호
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    • pp.3631-3636
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    • 2012
  • Objective: To determine whether silence of $PKC-{\alpha}$ expression by small interference RNA (siRNA) might regulate MDR1 expression and reverse chemoresistance of ovarian cancer. Methods: We measured gene and protein expression of MDR1 and $PKC-{\alpha}$ in ovarian cancer cells and assessed their correlation with cell drug resistance. We also examined whether blocking $PKC-{\alpha}$ by RNA interference (RNAi) affected MDR1 expression and reversed drug resistance in drug sensitivity tests. Results: The drug resistance cell lines, OV1228/DDP and OV1228/Taxol, had higher gene and protein expression of MDR1 and $PKC-{\alpha}$ than their counterpart sensitive cell line, OV1228. SiRNA depressed $PKC-{\alpha}$ gene protein expression, as well as MDR1 and protein expression and improved the drug sensitivity in OV1228/DDP and OV1228/Taxol cells. Conclusion: These results indicated that decreasing $PKC-{\alpha}$ expression with siRNA might be an effective method to improve drug sensitivity in drug resistant cells with elevated levels of $PKC-{\alpha}$ and MDR1. A new siRNA-based therapeutic strategy targeting $PKC-{\alpha}$ gene could be designed to overcome the chemoresistance of ovarian cancer.

Involvement of GRP78 in the Resistance of Ovarian Carcinoma Cells to Paclitaxel

  • Zhang, Li-Ying;Li, Pei-Ling;Xu, Aili;Zhang, Xin-Chen
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권8호
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    • pp.3517-3522
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    • 2015
  • Background: Glucose regulated protein 78 (GRP78) is a type of molecular chaperone. It is a possible candidate protein that contributes to development of drug resistance. We first examined the involvement of GRP78 in chemotherapy-resistance in human ovarian cancer cell. Materials and Methods: The expression of GRP78 mRNA and protein were examined by RT-PCR and western blotting, respectively, in human ovarian cancer cells line (HO-8910). Sensitivity of HO-8910 to paclitaxel was determined with methyl thiazolyl tetrazolium (MTT). Suppression of GRP78 expression was performed using specific small-interfering RNA (siRNA) in HO-8910 cells, and cell apoptosis was assessed by flow cytometry. Statistical analysis was performed using the SPSS 15.0 statistical package. Results: HO-8910 cells, with high basal levels of GRP78, exhibited low sensitivity to paclitaxel. The mRNA and protein levels of GRP78 were dramatically decreased at 24h, 48h and 72h after transfection and the sensitivity to paclitaxel was increased when the GRP78 gene was disturbed by specific siRNA transfection. Conclusions: The results suggested that high GRP78 expression might be one of the molecular mechanisms causing resistance to paclitaxel, and therefore siRNA of GRP78 may be useful in tumor-specific gene therapy for ovarian cancer.

Lactococcus lactis subsp. cremoris ATCC 11602-A1의 세포벽 구성분과 Phage 내성과의 관련성에 관한 연구 (The Relationship between the Cell Wall Components of Lactococcus lactis subsp.cremoris ATCC 11602-A1 and Its Bacteriophage Resistance)

  • 이춘화;배인휴;강국희
    • 한국미생물·생명공학회지
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    • 제22권3호
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    • pp.240-245
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    • 1994
  • Relation the phage defense mechanism of phage resistant Lactococcus lactis subsp. cremoris ATCC 11602-A1 to its cell wall components was investigated. To determine whether teichoic acid which is known to be one of the phage receptor site present on the cell wall, phage adsorption was examined after treatment 5% TCA(60%$\CIRC $C) and concanavalin A to the cell wall of A1 and parent strain. However, the adsorption rate of two strains did not change. Total amount of phosphate after TCA treatment did not change in both strains, but a difference between the two strains was observed. Ribitol and glycerol, components of teichoic acid, could not be detected in the cell walls of two strains by GC analysis. These results suggest that although teichoic acid was not present in the cell walls of both strains, the composition of cell wall of two strains was not identical. Measurement of amount of protein and SDS-polyacryamide gel electrophoresis were carried out to examine the involvement of cell wall protein in phage resistance, showing that protein is nothing to do with phage adsorption of parent strain, but phage resistance of A1 is related to protein. Cell wall carbohydrates of A1 contained rhamnose, glucose, and galactose. Total amount of carbohydrate of 1% SDS-treated A1 cell wall was reduced to the level of parent strain. The results suggest that phage resistance of A1 was due to the presence of a higher level of carbohydrates then parent strain, and to interaction of carbohydrate and protein.

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12주저항트레이닝 운동시 천연단백질과 분리유청단백질 섭취의 차이가 근육량 및 신체구성에 미치는 영향 (The Effect of the Difference Between Natural Protein and Whey Protein Intake During the 12 weeks of Resistance Training Exercise on Changes in Solt Lean Mass and Body Composltion)

  • 박원덕
    • 수산해양교육연구
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    • 제28권5호
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    • pp.1220-1230
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    • 2016
  • The purpose of this study is to investigate the effect of 20s university student bodybuilders' protein intake differences with resistant exercise(weight training) by 12 weeks on solt lean mass and body composltion. Natural protein(Chicken breast meat) intake group and Whey protein isolates(WPI) intake group are the experimental groups. Conventional meal intake group is the control group. This study proposes a efficient protein diet for weight training. The results were as follows. In the experimental group(natural protein intake), muscle mass and lean body mass was significantly increased, but body fat percentage was significantly decreased. In the experimental group(WPI intake), muscle mass and lean body mass was significantly increased, but body fat percentage was significantly decreased. In the control group(conventional meal intake), muscle mass and lean body mass was insignificantly increased, but body fat percentage was insignificantly decreased. In addition, there was not a significant difference among intake groups, and also not a differentiated effect between natural protein and WPI intake. In conclusion, natural protein and WPI made muscle mass and lean body mass rise, body fat percentage reduced effectively. Only WPI intake(without natural protein intake) was the efficient mean to increase muscle mass and lean body mass, and to decrease body fat percentage.

Induction of RNA-mediated Resistance to Papaya Ringspot Virus Type W

  • Krubphachaya, Pongrit;Juricek, Mila;Kertbundit, Sunee
    • BMB Reports
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    • 제40권3호
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    • pp.404-411
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    • 2007
  • Transformation of cantaloupes with the coat protein (cp) gene of papaya ringspot virus type W (PRSV-W), Thai isolate, was used to introduce virus resistance. Binary vectors containing either the full length coat protein coding region under control of the 35S CaMV promoter(pSA1175), or the inverted-repeat of a coat protein coding region (pSA1304), were constructed and used for Agrobacteriummediated transformation of cotyledonary explants of the cantaloupe cultivar Sun Lady. Four independent transgenic lines were obtained using pSA1304 and one using pSA1175. Integration of the PRSV-W cp gene into the genome of these transgenic lines was verified by PCR amplification, GUS assays and Southern blot hybridization. In vitro inoculation of these lines with PRSV-W revealed that whereas the line containing pSA1175 remained sensitive, the four lines containing pSA1304 were resistant. The presence of small RNA species, presumably siRNA, corresponding to regions of the viral cp gene in transgenic lines resistant to PRSV-W supports the involvement of post-transcriptional gene silencing in the establishment of resistance.