• Title/Summary/Keyword: Metabolic Pathways

Search Result 433, Processing Time 0.023 seconds

Insulin Induces Transcription of VEGF in Arnt-dependent but HIF-l$\alpha$-Independent Pathway

  • Park, Youngyeon;Park, Hyuns-Sung
    • Proceedings of the Korean Society of Applied Pharmacology
    • /
    • 2001.11a
    • /
    • pp.100-100
    • /
    • 2001
  • Hypoxia is a pathophysiological condition that occurs during injury, ischemia, and stroke. Hypoxic stress induces the expression of genes associated with increased energy flux, including the glucose transporters Glutl and Glut3, several glycolytic enzymes, nitric oxide synthase, erythropoietin and vascular endothelial growth factor. Induction of these genes is mediated by a common basic helix-loop-helix PAS transcription complex, the hypoxia-inducible factor-l${\alpha}$ (HIF-1${\alpha}$)/ aryl hydrocarbon receptor nuclear translocator (ARNT). Insulin plays a central role in regulating metabolic pathways associated with energy storage and utilization. It triggers the conversion of glucose into glycogen and triglycerides and inhibits gluconeogenesis. Insulin also induced hypoxia-induced genes. However the underlying mechanism is unestablished. Here, we study the possibility that transcription factor HIF-1${\alpha}$ is involved in insulin-induced gene expression. We investigate the mechanism that regulates hypoxia-inducible gene expression In response to insulin We demonstrate that insulin increases the transcription of hypoxia- inducible gene. Insulin-induced transcription is not detected in Arnt defective cell lines. Under hypoxic condition, HIF- l${\alpha}$ stabilizes but does not under insulin treatment. Insulin-induced gene expression is inhibited by presence of PI-3 kinase inhibitor and Akt dominant negative mutant, whereas hypoxia-induced gene expression is not. ROS inhibitor differently affects insulin-induced gene expressions and hypoxia-induced gene expressions. Our results demonstrate that insulin also regulates hypoxia-inducible gene expression and this process is dependent on Arnt. However we suggest HIF-l${\alpha}$ is not involved insulin-induced gene expression and insulin- and hypoxia- induces same target genes via different signaling pathway.

  • PDF

Discovering Novel Genes of poultry in Genomic Era

  • S.K. Kang;Lee, B.C.;J.M. Lim;J.Y. Han;W.S. Hwang
    • Korean Journal of Poultry Science
    • /
    • v.28 no.2
    • /
    • pp.143-153
    • /
    • 2001
  • Using bioinformatic tools for searching the massive genome databases, it is possible to Identify new genes in few minutes for initial discoveries based on evolutionary conservation, domain homology, and tissue expression patterns, followed by further verification and characterization using the bench-top works. The development of high-density two-dimensional arrays has allowed the analysis of the expression of thousands of genes simultaneously in the humans, mice, rats, yeast, and bacteria to elucidate the genes and pathways involved in physiological processes. In addition, rapid and automated protein identification is being achieved by searching protein and nucleotide sequence databases directly with data generated from mass spectrometry. Recently, analysis at the bio-chemical level such as biochemical screening and metabolic profiling (Biochemical genomics) has been introduced as an additional approach for categorical assignment of gene function. To make advantage of recent achievements in computational approaches for facilitated gene discoveries in the avian model, chicken expression sequence tags (ESTs) have been reported and deposited in the international databases. By searching EST databases, a chicken heparanase gene was identified and functionally confirmed by subsequent experiments. Using combination of sub-tractive hybridization assay and Genbank database searches, a chicken heme -binding protein family (cSOUL/HBP) was isolated in the retina and pineal gland of domestic chicken and verified by Northern blot analysis. Microarrays have identified several host genes whose expression levels are elevated following infection of chicken embryo fibroblasts (CEF) with Marek's disease virus (MDV). The ongoing process of chicken genome projects and new discoveries and breakthroughs in genomics and proteomics will no doubt reveal new and exciting information and advances in the avian research.

  • PDF

Physical Activity and its Relation to Cancer Risk: Updating the Evidence

  • Kruk, Joanna;Czerniak, Urszula
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.14 no.7
    • /
    • pp.3993-4003
    • /
    • 2013
  • Scientific evidence for the primary prevention of cancer caused by physical activity of regular moderate-intensity or greater is rapidly accumulating in this field. About 300 epidemiologic studies on the association between physical activity and cancer risk have been conducted worldwide. The objectives of this paper were three-fold: (i) to describe briefly the components of physical activity and its quantification; (ii) to summarize the most important conclusions available from comprehensive reports, and reviews of the epidemiologic individual and intervention studies on a role physical activity in cancer prevention; (iii) to present proposed biological mechanisms accounting for effects of activity on cancer risk. The evidence of causal linked physical activity and cancer risk is found to be strong for colon cancer - convincing; weaker for postmenopausal breast and endometrium cancers - probable; and limited suggestive for premenopausal breast, lung, prostate, ovary, gastric and pancreatic cancers. The average risk reductions were reported to be 20-30%. The protective effects of physical activity on cancer risk are hypothesized to be through multiple interrelated pathways: decrease in adiposity, decrease in sexual and metabolic hormones, changes in biomarkers and insulin resistance, improvement of immune function, and reduction of inflammation. As there are several gaps in the literature for associations between activity and cancer risk, additional studies are needed. Future research should include studies dealing with limitations in precise estimates of physical activity and of a lack of consensus on what defines sedentary behavior of individuals and those linked with the proposed biomarkers to cancer risk and controlled exercise intervention trials.

Effects of Amomum cadamomum Linne Extract on TNF-α-induced Inflammation and Insulin Resistance in 3T3-L1 Adipocytes

  • Kang, Kyung-Hwa;Song, Choon-Ho
    • Journal of Physiology & Pathology in Korean Medicine
    • /
    • v.30 no.1
    • /
    • pp.54-60
    • /
    • 2016
  • Amomum cadamomum Linne (ACL) has long been utilized against the inhibited qi movement related diseases such as dyspepsia, acute gastroenteritis, vomiting and diarrhea in Korean medicine. We speculated that ACL could improve the metabolic disorders such as obesity and type 2 diabetes through removing the phlegm-dampness and promoting the qi movement or stagnation. This study was designed to investigate effects and molecular mechanisms of ACL extract on the improvement of adipocyte dysfunction induced by TNF-α in 3T3-L1 adipocytes. Potential roles of ACL extract in the lipogenesis, inhibition of inflammatory cytokines and insulin resistance, were investigated in this study. Also, we examined the adipose genes and signaling molecules related to insulin resistance and glucose uptake to elucidate its mechanism. Our data demonstrated that TNF-α significantly incresed the release of lipid droplets and the production of MCP-1 and IL-6 from adipocytes. In gene expression, TNF-α reduced the expression of aP2, PPARγ, C/EBPα, GLUT4, and IRS-1 related to lipogenesis and insulin sesitivity, while TNF-α increased the expression of MCP-1 related to inflammation. In addition, TNF-α down-regulated the PPARγ and IRS-1 protein and up-regulated the IRS-1 Ser307 phosphorylation. These alterations induced by TNF-α were prevented by the treatment of ACL extract. Thus, our results indicate that ACL extract can be used to prevent from the TNF-α-induced adipocyte dysfunction through insulin and PPARγ pathways.

Biological Aspects of Selenium in Farm Animals

  • Kim, Y.Y.;Mahan, D.C.
    • Asian-Australasian Journal of Animal Sciences
    • /
    • v.16 no.3
    • /
    • pp.435-444
    • /
    • 2003
  • In 1957, Schwarz and Foltz discovered that selenium (Se) was an essential trace mineral and nutritionists then started extensive studies to figure out the metabolic function of this element which has been called as toxic mineral. The discovery that glutathione peroxidase (GSH-Px) contained Se demonstrated a biochemical role for Se as an essential trace element. The major physiological function of Se containing GSH-Px is thought to maintain low levels of $H_2O_2$ and other hydroperoxides in the cell to prevent tissues from peroxidation damages. It is known that the GSH-Px activity is increased when animals were fed high dietary levels of Se. Chemical properties of Se have much in common with sulfur (S) therefore Se would follow the sulfur pathways in its metabolism in animal body. Two sources of Se are available for supplementation of Se in animal feed. Inorganic Se can also exist in selenide (-2), elemental (0), selenite (+4) and selenate (+6) oxidation state with other minerals. When sulfur in S containing amino acids is replaced by Se, organic Se can be made and named "eleno"prior to the name of S containing amino acid, i.e. selenomethionine. Selenium deficiency affects humans as well as animals and dysfunctions such as exudative diathesis, retained placenta, mastitis, liver necrosis, Keshan disease, numerous diseases and cancer. From several centuries ago, Se toxicity was recognized in various animal species and much of the current toxic Se levels has been established largely based upon the controlled toxicity studies used inorganic Se. Toxic effects of Se in animal result in reduced feed intake, growth retardation, ataxia, diarrhea, alopecia and sloughing of hooves. However, several experiments demonstrated that Se deficiencies or toxicities were varied by dietary Se levels and sources. Recent studies demonstrated that the incidence of colorectal and prostate cancer was reduced by approximately 50% when humans consumed 200 ${\mu}g$ of Se daily.

Identifying Differentially Expressed Genes and Small Molecule Drugs for Prostate Cancer by a Bioinformatics Strategy

  • Li, Jian;Xu, Ya-Hong;Lu, Yi;Ma, Xiao-Ping;Chen, Ping;Luo, Shun-Wen;Jia, Zhi-Gang;Liu, Yang;Guo, Yu
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.14 no.9
    • /
    • pp.5281-5286
    • /
    • 2013
  • Purpose: Prostate cancer caused by the abnormal disorderly growth of prostatic acinar cells is the most prevalent cancer of men in western countries. We aimed to screen out differentially expressed genes (DEGs) and explore small molecule drugs for prostate cancer. Materials and Methods: The GSE3824 gene expression profile of prostate cancer was downloaded from Gene Expression Omnibus database which including 21 normal samples and 18 prostate cancer cells. The DEGs were identified by Limma package in R language and gene ontology and pathway enrichment analyses were performed. In addition, potential regulatory microRNAs and the target sites of the transcription factors were screened out based on the molecular signature database. In addition, the DEGs were mapped to the connectivity map database to identify potential small molecule drugs. Results: A total of 6,588 genes were filtered as DEGs between normal and prostate cancer samples. Examples such as ITGB6, ITGB3, ITGAV and ITGA2 may induce prostate cancer through actions on the focal adhesion pathway. Furthermore, the transcription factor, SP1, and its target genes ARHGAP26 and USF1 were identified. The most significant microRNA, MIR-506, was screened and found to regulate genes including ITGB1 and ITGB3. Additionally, small molecules MS-275, 8-azaguanine and pyrvinium were discovered to have the potential to repair the disordered metabolic pathways, abd furthermore to remedy prostate cancer. Conclusions: The results of our analysis bear on the mechanism of prostate cancer and allow screening for small molecular drugs for this cancer. The findings have the potential for future use in the clinic for treatment of prostate cancer.

Glyceraldehyde-3-Phosphate, a Glycolytic Intermediate, Prevents Cells from Apoptosis by Lowering S-Nitrosylation of Glyceraldehyde-3-Phosphate Dehydrogenase

  • Lee, Sun-Young;Kim, Jeong-Hoon;Jung, Hye-Yun;Chi, Seung-Wook;Chung, Sang-J.;Lee, Chong-Kil;Park, Byoung-Chul;Bae, Kwang-Hee;Park, Sung-Goo
    • Journal of Microbiology and Biotechnology
    • /
    • v.22 no.4
    • /
    • pp.571-573
    • /
    • 2012
  • Glyceraldehyde-3-phosphate (G-3-P), the substrate of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), is a key intermediate in several metabolic pathways. Recently, we reported that G-3-P directly inhibits caspase-3 activity in a reversible noncompetitive mode, suggesting the intracellular G-3-P level as a cell fate decision factor. It has been known that apoptotic stimuli induce the generation of NO, and NO S-nitrosylates GAPDH at the catalytic cysteine residue, which confers GAPDH the ability to bind to Siah-1, an E3 ubiquitin ligase. The GAPDH-Siah-1 complex is translocated into the nucleus and subsequently triggers the apoptotic process. Here, we clearly showed that intracellular G-3-P protects GAPDH from S-nitrosylation at above a certain level, and consequently maintains the cell survival. In case G-3-P drops below a certain level as a result of exposure to specific stimuli, G-3-P cannot inhibit S-nitrosylation of GAPDH anymore, and consequently GAPDH translocates with Siah-1 into the nucleus. Based on these results, we suggest that G-3-P functions as a molecule switch between cell survival and apoptosis by regulating S-nitrosylation of GAPDH.

Extended latex proteome analysis deciphers additional roles of the lettuce laticifer

  • Cho, Won-Kyong;Chen, Xiong-Yan;Rim, Yeong-Gil;Chu, Hyo-Sub;Jo, Yeon-Hwa;Kim, Su-Wha;Park, Zee-Yong;Kim, Jae-Yean
    • Plant Biotechnology Reports
    • /
    • v.4 no.4
    • /
    • pp.311-319
    • /
    • 2010
  • Lettuce is an economically important leafy vegetable that accumulates a milk-like sap called latex in the laticifer. Previously, we conducted a large-scale lettuce latex proteomic analysis. However, the identified proteins were obtained only from lettuce ESTs and proteins deposited in NCBI databases. To extend the number of known latex proteins, we carried out an analysis identifying 302 additional proteins that were matched to the NCBI non-redundant protein database. Interestingly, the newly identified proteins were not recovered from lettuce EST and protein databases, indicating the usefulness of this hetero system in MudPIT analysis. Gene ontology studies revealed that the newly identified latex proteins are involved in many processes, including many metabolic pathways, binding functions, stress responses, developmental processes, protein metabolism, transport and signal transduction. Application of the non-redundant plant protein database led to the identification of an increased number of latex proteins. These newly identified latex proteins provide a rich source of information for laticifer research.

Current status on expression profiling using rice microarray (벼 microarray를 이용한 유전자발현 profiling 연구동향)

  • Yoon, Ung-Han;Kim, Yeon-Ki;Kim, Chang-Kug;Hahn, Jang-Ho;Kim, Dong-Hern;Lee, Tae-Ho;Lee, Gang-Seob;Park, Soo-Chul;Nahm, Baek-Hie
    • Journal of Plant Biotechnology
    • /
    • v.37 no.2
    • /
    • pp.144-152
    • /
    • 2010
  • As the International Rice Genome Sequencing Project (IRGSP) was completed in 2005 and opened to the public, many countries are making a lot of investments in researches on the utilization of sequence information along with system development. Also, the necessity of the functional genomics researches using microarray is increased currently to secure unique genes related with major agricultural traits and analyze metabolic pathways. Microrarray enables efficient analysis of large scale gene expression and related transcription regulation. This review aims to introduce available microarrays made based on rice genome information and current status of gene expression analysis using these microarrays integrated with the databases available to the public. Also, we introduce the researches on the large scale functional analysis of genes related with useful traits and genetic networks. Understanding of the mechanism related with mutual interaction between proteins with co-expression among rice genes can be utilized in the researches for improving major agricultural traits. The direct and indirect interactions of various genes would provide new functionality of rice. The recent results of the various expression profiling analysis in rice will promote functional genomic researches in plants including rice and provide the scientists involved in applications researches with wide variety of expression informations.

De novo gene set assembly of the transcriptome of diploid, oilseed-crop species Perilla citriodora

  • Kim, Ji-Eun;Choe, Junkyoung;Lee, Woo Kyung;Kim, Sangmi;Lee, Myoung Hee;Kim, Tae-Ho;Jo, Sung-Hwan;Lee, Jeong Hee
    • Journal of Plant Biotechnology
    • /
    • v.43 no.3
    • /
    • pp.293-301
    • /
    • 2016
  • High-quality gene sets are necessary for functional research of genes. Although Perilla is a commonly cultivated oil crop and vegetable crop in Southeast Asia, the quality of its available gene set is insufficient. To construct a high-quality Perilla gene set, we sequenced mRNAs extracted from different tissues of Perilla citriodora, the wild species (2n = 20) of Perilla. To make a high-quality gene set for P. citriodora, we compared the quality of assemblies produced by Velvet and Trinity, the two well-known de novo assemblers, and improved the de novo assembly pipeline by optimizing k-mers and removing redundant sequences. We then selected representative transcripts for loci according to several criteria. The improved assembly yielded a total of 86,396 transcripts and 38,413 representative transcripts. We evaluated the assembled transcripts by comparing them to 638 homologous Arabidopsis genes involved in fatty acid and TAG biosynthesis pathways. High proportions of full-length genes and transcripts in the assembled transcripts matched known genes in other species, indicating that the P. citriodora gene set can be applied in future functional studies. Our study provides a reference P. citriodora gene set for further studies. It will serve as valuable genetic resource to elucidate the molecular basis of various metabolisms.