• Genomics & Informatics
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• 제7권2호
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• pp.53-56
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• 2009

Recent evidence has strongly suggested that the CAP/TC10 pathway is involved in the trafficking, docking, and fusion of vesicles containing the insulin-responsive glucose transporter Glut4 to the plasma membrane. However, little is known about how the genes employed in the CAP/TC10 pathway are associated with the development of type 2 diabetes mellitus. In this study, we sequenced 4 genes of the CAP/TC10 pathway [SORBS1, CBL, CRK, and RHOQ] in 24 individuals to identify genetic variations in these loci. A total of 48 sequence variants were identified, including 23 novel variations. To investigate the possible association with type 2 diabetes mellitus, 3 single nucleotide polymorphisms from SORBS1, 3 from CBL, and 4 from RHOQ were genotyped in 1122 Korean type 2 diabetic patients and 1138 nondiabetic controls. Using logistic regression analysis, 1 significant association between SNP rs1376405 in RHOQ and type 2 diabetes mellitus [OR = 8.714 (C.I. 1.714-44.29), p = 0.009] was found in the recessive model. Our data demonstrate a positive association of the RHOQ gene in the CAP/TC10 pathway with T2DM in the Korean population.

• BMB Reports
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• 제52권7호
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• pp.457-462
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• 2019

[18F]Fluorodeoxyglucose (FDG) PET/CT imaging has been widely used in the diagnosis of malignant tumors. ATPase family AAA domain-containing protein 2 (ATAD2) plays important roles in tumor growth, invasion and metastasis. However, the relationship between [18F]FDG accumulation and ATAD2 expression remains largely unknown. This study aimed to investigate the correlation between ATAD2 expression and [18F]FDG uptake in lung adenocarcinoma (LUAD), and elucidate its underlying molecular mechanisms. The results showed that ATAD2 expression was positively correlated with maximum standardized uptake value ($SUV_{max}$), total lesion glycolysis (TLG), glucose transporter type 1 (GLUT1) expression and hexokinase2 (HK2) expression in LUAD tissues. In addition, ATAD2 knockdown significantly inhibited the proliferation, tumorigenicity, migration, [18F]FDG uptake and lactate production of LUAD cells, while, ATAD2 overexpression exhibited the opposite effects. Furthermore, ATAD2 modulated the glycometabolism of LUAD via AKT-GLUT1/HK2 pathway, as assessed using LY294002 (an inhibitor of PI3K/AKT pathway). In summary, to explore the correlation between ATAD2 expression and glycometabolism is expected to bring good news for anti-energy metabolism therapy of cancers.

• Asian-Australasian Journal of Animal Sciences
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• 제26권8호
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• pp.1189-1196
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• 2013

Adipose tissue development and function play a critical role in the regulation of energy balance, lipid metabolism, and the pathophysiology of metabolic syndromes. Although the effect of zinc ascorbate supplementation in diabetes or glycemic control is known in humans, the underlying mechanism is not well described. Here, we investigated the effect of a zinc-chelated vitamin C (ZnC) compound on the adipogenic differentiation of 3T3-L1 preadipocytes. Treatment with ZnC for 8 d significantly promoted adipogenesis, which was characterized by increased glycerol-3-phosphate dehydrogenase activity and intracellular lipid accumulation in 3T3-L1 cells. Meanwhile, ZnC induced a pronounced up-regulation of the expression of glucose transporter type 4 (GLUT4) and the adipocyte-specific gene adipocyte protein 2 (aP2). Analysis of mRNA and protein levels further showed that ZnC increased the sequential expression of peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) and CCAAT/enhancer-binding protein alpha (C/$EBP{\alpha}$), the key transcription factors of adipogenesis. These results indicate that ZnC could promote adipogenesis through $PPAR{\gamma}$ and C/$EBP{\alpha}$, which act synergistically for the expression of aP2 and GLUT4, leading to the generation of insulin-responsive adipocytes and can thereby be useful as a novel therapeutic agent for the management of diabetes and related metabolic disorders.

• BMB Reports
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• 제39권1호
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• pp.26-36
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• 2006

Differential Display PCR technique (DD-PCR) was used for the analysis of altered gene expression in hemocytes of Vibrio harveyi-infected Penaeus monodon. Forty-four combinations of arbitrary and oligo(dT) primers were used to screen for differentially expressed genes. A total of 79 differentially expressed bands could be identified from 33 primer combinations. These included 48 bands (61%) whose expression level increased and 31 bands (39%) decreased after V. harveyi challenge. Subsequently, forty-eight differential display fragments were successfully reamplified and cloned. A total of 267 clones were randomly selected and sequenced. The sequence analysis showed that 85 (31%) out of 267 clones were matched with sequences in the GenBank database which represented 24 different genes with known functions. Among the known genes, glucose transporter 1, interferon-related developmental regulator 1, lysozyme, profilin, SERPINB3, were selected for further confirmation of their differentially expression patterns by real-time PCR. The results showed increasing in expression level of the selected genes in shrimp hemocytes after microbial challenge suggesting the involvement of such genes in bacterial response in shrimp. The anti-lipopolysaccharide factor type 3 (ALFPm3) gene, previously reported in P. monodon (Supungul et al., 2002) was found among the up-regulated genes but diversity due to amino acid changes was observed. Increase in ALFPm3 transcripts upon V. harveyi injection is in accordance with that found in the previous study.

• Journal of Microbiology and Biotechnology
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• 제17권6호
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• pp.934-944
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• 2007

Paenibacillus polymyxa E681 is known to be able to suppress plant diseases by producing antimicrobial compounds and to promote plant growth by producing phytohormones, and secreting diverse degrading enzymes. In spite of these capabilities, little is known regarding the flow of information from the bacterial strain to the barley roots. In an attempt to determine the flow of information from the bacterial strain to barley roots, the strain was grown in the presence and absence of barley, and two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and MALDI-TOF mass spectrometry were used. 2D-PAGE detected approximately 1,000 spots in the cell and 1,100 spots in the supernatant at a pH 4-10 gradient. Interestingly, about 80 spots from each sample showed quantitative variations. Fifty-three spots from these were analyzed by MALDI-TOF mass spectrometry and 28 proteins were identified. Most of the cytosolic proteins expressed at higher levels were found in P. polymyxa E681 cells grown in the presence of barley rather than in the absence of barley. Proteins detected at a lower level in the surpernatant of P. polymyxa E68l cells grown in the presence of barley were lipoprotein, glucose-6-phosphate 1-dehydrogenase, heat-shock protein HtpG, spermidine synthase, OrfZ, ribonuclease PH, and coenzyme PQQ synthesis protein, and flagellar hook-associated protein 2 whereas proteins detected at a higher level in the surpernatant of P. polymyxa E681 cells grown in the presence of barley included D-alanyl-D-alanine ligase A, isopentenyl-diphosphate delta-isomerase, ABC transporter ATP-binding protein Uup, lipase. Many of the proteins belonging to plant-induced stimulons are associated with biosynthetic metabolism and metabolites of proteins and transport. Some of these proteins would be expected to be induced by environmental changes resulting from the accumulation of plant-secreted substances.

• Journal of Animal Science and Technology
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• 제63권6호
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• pp.1397-1410
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• 2021

The present study was designed to determine the influence of all-trans retinoic acid (ATRA) on adipogenesis-related gene regulation in bovine intramuscular (IM) and subcutaneous (SC) adipose cells during differentiation. Bovine IM and SC adipocytes were isolated from three 19-mo-old, crossbred steers. Adipogenic differentiation was induced upon cultured IM and SC preadipocytes with various doses (0, 0.001, 0.01, 0.1, 1 µM) of ATRA. After 96 h of incubation, cells were harvested and used to measure the gene expression of CCAAT/Enhancer binding protein β (C/EBPβ), peroxisome proliferator-activated receptor (PPAR) γ, glucose transporter 4 (GLUT4), stearoyl CoA desaturase (SCD), and Smad transcription factor 3 (Smad3) relative to the quantity of ribosomal protein subunit 9 (RPS 9). Retinoic acid receptor (RAR) antagonist also tested to identify the effect of ATRA on PPARγ -RAR related gene expression in IM cells. The addition of ATRA to bovine IM decreased (p < 0.05) expression of PPARγ. The expression of PPARγ was also tended to be downregulated (p < 0.1) in high levels (10 µM) of ATRA treatment in SC cells. The treatment of RAR antagonist increased the expression of PPARγ in IM cells. Expression of C/EBPβ decreased (p < 0.05) in SC, but no change was observed in IM (p > 0.05). Increasing levels of ATRA may block adipogenic differentiation via transcriptional regulation of PPARγ. The efficacy of ATRA treatment in adipose cells may vary depending on the location.

• Journal of Gastric Cancer
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• 제20권1호
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• pp.60-71
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• 2020

Purpose: The utility of 18-fluordesoxyglucose positron emission tomography ([¹⁸F]-FDG-PET) combined with computer tomography or magnetic resonance imaging (MRI) in gastric cancer remains controversial and a rationale for patient selection is desired. This study aims to establish a preclinical patient-derived xenograft (PDX) based [¹⁸F]-FDG-PET/MRI protocol for gastric cancer and compare different PDX models regarding tumor growth and FDG uptake. Materials and Methods: Female BALB/c nu/nu mice were implanted orthotopically and subcutaneously with gastric cancer PDX. [¹⁸F]-FDG-PET/MRI scanning protocol evaluation included different tumor sizes, FDG doses, scanning intervals, and organ-specific uptake. FDG avidity of similar PDX cases were compared between ortho- and heterotopic tumor implantation methods. Microscopic and immunohistochemical investigations were performed to confirm tumor growth and correlate the glycolysis markers glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) with FDG uptake. Results: Organ-specific uptake analysis showed specific FDG avidity of the tumor tissue. Standard scanning protocol was determined to include 150 μCi FDG injection dose and scanning after one hour. Comparison of heterotopic and orthotopic implanted mice revealed a long growth interval for orthotopic models with a high uptake in similar PDX tissues. The H-score of GLUT1 and HK2 expression in tumor cells correlated with the measured maximal standardized uptake value values (GLUT1: Pearson r=0.743, P=0.009; HK2: Pearson r=0.605, P=0.049). Conclusions: This preclinical gastric cancer PDX based [¹⁸F]-FDG-PET/MRI protocol reveals tumor specific FDG uptake and shows correlation to glucose metabolic proteins. Our findings provide a PET/MRI PDX model that can be applicable for translational gastric cancer research.

• 한방비만학회지
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• 제24권1호
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• pp.25-40
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• 2024

Objectives: In the present study, we investigated the effects of clean-diabetes mellitus 3 (C-DM3), a herbal formula with Trichosanthis Radix, Coptidis Rhizoma, Crataegi Fructus, and Cinnamomi Cortex, on the pathological and serological symptoms of diabetes and its related molecular mechanisms in diet-induced obese mice. Methods: We prepared an obese mouse model using a high-fat diet for 8 weeks and then administered the C-DM3 extract for 4 weeks. The changes of pathological and serological biomarkers for diabetes assessment were measured in the mice and histological changes were observed in the liver and pancreas tissues. We also identified the main compounds in the C-DM3 extract using high pressure liquid chromatography (HPLC) and analyzed the molecular mechanism of the disease condition by network pharmacological analysis. Results: In the in vivo, the administration of C-DM extract to obese mice significantly reduced body weight gain, fatty liver symptoms, and muscle loss, and decreased the levels of fasting blood glucose, insulin, aspertate aminotransferase, triglycerides, and low-density lipoprotein-cholesterol. In addition, C-DM extract significantly increased the phosphorylation of insulin receptor substrate 1, protein kinase b (AKT), phosphoinositide 3-kinase (PI3K), adenosine monophosphate-activated protein kinase, and glucose transporter 4 in all pancreatic and liver tissues, with inhibition of histopathological changes in obese mice. HPLC analysis identified hyperoside, berberine, epiberberine, columbamin, coptisine, coumarin, jatrorrhizine, and citric acid as the main compounds. In the network pharmacological analysis, the molecular targets of C-DM3 extract on obesity and diabetes were shown as the insulin, AKT, PI3K, and mitogen-activated protein kinase pathways with the regulation of inflammatory molecules interleukin 6 (IL-6), jun proto-oncogene, and IL-1β, which matched our in vivo targets. Conclusions: Based on these results, C-DM3 extract is expected to be effective in improving obesity and preventing diabetic progression.

• Journal of Microbiology and Biotechnology
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• 제21권2호
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• pp.162-169
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• 2011

A dynamic model of lactic acid fermentation using Lactococcus lactis was constructed, and a metabolic flux analysis (MFA) and metabolic control analysis (MCA) were performed to reveal an intensive metabolic understanding of lactic acid bacteria (LAB). The parameter estimation was conducted with COPASI software to construct a more accurate metabolic model. The experimental data used in the parameter estimation were obtained from an LC-MS/MS analysis and time-course simulation study. The MFA results were a reasonable explanation of the experimental data. Through the parameter estimation, the metabolic system of lactic acid bacteria can be thoroughly understood through comparisons with the original parameters. The coefficients derived from the MCA indicated that the reaction rate of L-lactate dehydrogenase was activated by fructose 1,6-bisphosphate and pyruvate, and pyruvate appeared to be a stronger activator of L-lactate dehydrogenase than fructose 1,6-bisphosphate. Additionally, pyruvate acted as an inhibitor to pyruvate kinase and the phosphotransferase system. Glucose 6-phosphate and phosphoenolpyruvate showed activation effects on pyruvate kinase. Hexose transporter was the strongest effector on the flux through L-lactate dehydrogenase. The concentration control coefficient (CCC) showed similar results to the flux control coefficient (FCC).

• 한국미생물·생명공학회지
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• 제44권4호
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• pp.563-570
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• 2016

S. griseus wild type에서 dasA 유전자의 과발현에 의해 유도된 기저균사의 ectopic sporulation 관련 유전자를 알아보기 위해서, empty vector가 삽입된 균주와 dasA가 과발현된 균주의 전사체를 DNA microarray법으로 비교하였다. DNA microarray 결과를 토대로 dasA 유전자 과발현 균주에서 2배이상 발현량이 증가되었으며 p-value가 0.05 미만(p-value < 0.05)인 유전자들 중에서 false positive 를 제외시키는 작업을 통하여 최종적으로 4개의 유전자(SGR794, SGR2469, SGR3656, SGR3657)와 3개의 cluster (SGR795-797, SGR2377-2378, SGR6997-6998)를 선발하였다. 이들의 전사량은 low resolution Sl nuclease mapping 법을 통하여 dasA 유전자 과발현 균주에서 증가된 것을 확인하였다.