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The Metabolic Effects of FGF21: From Physiology to Pharmacology (생리, 약학적 관점에서 fibroblast growth factor 21 (FGF21)의 대사 효과 고찰)

  • Song, Parkyong
    • Journal of Life Science
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    • v.30 no.7
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    • pp.640-650
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    • 2020
  • Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF protein family which is highly synthesized in the liver, pancreas, and adipose tissue. Depending on the expression tissue, FGF21 uses endo- or paracrine features to regulate several metabolic pathways including glucose metabolism and energy homeostasis. Different physiologically stressful conditions such as starvation, a ketogenic diet, extreme cold, and mitochondrial dysfunction are known to induce FGF21 synthesis in various tissues to exert either adaptive or defensive mechanisms. More specifically, peroxisome proliferator-activated receptor gamma and peroxisome proliferator-activated receptor alpha control FGF21 expression in adipose tissue and liver, respectively. In addition, the pharmacologic administration of FGF21 has been reported to decrease the body weight and improve the insulin sensitivity and lipoprotein profiles of obese mice and type 2 diabetes patients meaning that FGF21 has attracted huge interest as a therapeutic agent for type 2 diabetes, obesity, and non-alcoholic fatty liver disease. However, understanding FGF21 remains complicated due to the paradoxical condition of its tissue-dependent expression. For example, nutrient deprivation largely increases hepatic FGF21 levels whereas adipose tissue-derived FGF21 is increased under feeding condition. This review discusses the issues of interest that have arisen from existing publications, including the tissue-specific function of FGF21 and its action mechanism. We also summarize the current stage of a clinical trial using several FGF21 analogs.

The lyophilization and stability of Salmonella typhi Ty21a (Salmonella thphi Ty21a의 동결 건조와 안정성)

  • 김세란;박동우;전홍렬;김희준;한성순;김기호;김홍진
    • YAKHAK HOEJI
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    • v.43 no.6
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    • pp.793-797
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    • 1999
  • Salmonella typhi Ty21a is an attenuated strain of S. typhimurium and used for oral typhoid vaccine. In an attempt to increase the stability of Ty21a manufacturing typhoid vaccine, we studied about the stability of freeze-dried Th21a including additives at various temperature conditions. In order to investigate the freeze-drying rate of Ty21a according to various absorbance, we lyophilized Ty21a by using 8% sucrose as a stabilizer. The optimal freeze-drying rate of Ty21a was appeared when OD (optical density) value of the growth was between 2.5 and 3.0. To investigate the stability of Ty21a at various temperature, the viability was measured after storaging the freeze-dried Ty21a at the room temperature, cold and freezing condition for 1 week. The viability of Ty21a in cold and freezing storage condition was 5 times more stable than in room temperature. To search the most stable additives for the freeze-dried Ty21a, the viability of Ty21a including additives at the various storage condition was estimated. Mannitol and loctose were the most stable additives. Theses results suggest that the OD value of Ty21a growth, low temperature, mannitol and lactose are important factors for the optimal freeze-drying rate, the stable storage and the most stable additives, respectively.

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Loss of Heterozygosity on the Long Arm of Chromosome 21 in Non-Small Cell Lung Cancer (비소세포폐암에서 21q 이형체 소실)

  • Chai, Po-Hee;Bae, Nack-Cheon;Lee, Eung-Bae;Park, Jae-Yong;Kang, Kyung-Hee;Kim, Kyung-Rok;Bae, Moon-Seob;Cha, Seung-Ik;Chae, Sang-Chul;Kim, Chang-Ho;Jung, Tae-Hoon
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.6
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    • pp.668-675
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    • 2001
  • Background : Non-smalll lung cancer(NSCLC) develops as a result of the accumulation of multiple genetic abnormalities. Loss of heterozygosity(LOH) is one of the most frequent genetic alterations that is found in NSCLC, and the chromosomal regions that display a high rate of LOH are thought to harbor tumor suppressor genes(TSGs). This study was done to determine the frequency of LOH in 21q with the aim of identifying potential TSG loci. Method : Thirty-nine surgically resected NSCLCs were analysed. Patients peripheral lymphocytes were used as the source of the normal DNA. Five microsatellite Inarkers of 21q were used to study LOH : 21q21.1(D21S1432, and D21S1994); 21q21.2-21.3(D21S1442) ; 21q22.1(21S1445) ; and 21q22.2-22.3(D21S266). The fractional allelic loss(FAL) in a tumor was calculated as the ratio of the number of markers showing LOH to the number of informative markers. Result : LOH for at least one locus was detected in 21 of 39 tumors(53.8%). Among the 21 tumors with LOH, 5(21.8%) showed LOH at almost all informative loci. Although statistically not significant, LOH was found more frequently in squamous cell carcinomas(15 of 23, 65.2%) than in adenocarcinomas(6 of 16, 37.5%). In the squamous cell carcinomas the frequency of LOH was higher in stage II-III (80.0%) than in stage I (53.8%). The FAL value in squamous cell carcinomas($0.431{\pm}0.375$) was significantly higher than that found in adenocarcinomas($0.l92{\pm}0.276$). Conclusion : These results suggest that LOH on 21q may be involved in the development of NSCLC, and that TSG(s) that contribute to the pathogenesis of NSCLC may exist on 21q.

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Pcp-2 Interacts Directly with Kinesin Superfamily KIF21A Protein (Kinesin superfamily KIF21A와 직접 결합하는 Pcp-2의 규명)

  • Park, Hye-Young;Kim, Sang-Jin;Ye, Sung-Su;Jang, Won-Hee;Lee, Sang-Kyeong;Park, Yeong-Hong;Jung, Yong-Wook;Moon, Il-Soo;Kim, Moo-Seong;Seog, Dae-Hyun
    • Journal of Life Science
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    • v.18 no.8
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    • pp.1059-1065
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    • 2008
  • KIF21A is a member of the Kinesin superfamily proteins (KIFs), which are microtubule-dependent molecular motors, anterograde axonal transporters of cargoes. Recently, congenital fibrosis of the extraocular muscles 1 (CFEOM1) has been shown to result from a small number of recurrent heterozygous missense mutations of KIF21A. CFEOM1 results from the inability of mutated KIF21A to successfully deliver cargoes to the development of the occulo-motor neuron or neuromuscular junction. Here, we used an yeast two-hybrid system to identify a protein that interacts with the WD-40 repeat domain of KIF21A and found a specific interaction with Purkinje cell protein-2 (Pcp-2), a small protein also known as L7. Pcp-2 protein bound to the WD-40 domain of KIF21A and KIF21B but not to other KIFs in yeast two-hybrid assays. In addition, this specific interaction was also observed in the glutathione S-transferase pull-down assay. An antibody to Pcp-2 specifically co-immunoprecipitated KIF21A associated with Pcp-2 from mouse brain extracts. These results suggest that Pcp-2 may be involved in the KIF21A-mediated transport as a KIF21A adaptor protein.