Induction of a hypermetabolic state in cultured hepatocytes by glucagon and H2O2.

Abstract:

:Stress hormones and pro-inflammatory cytokines are putative signals triggering increased energy expenditure or "hypermetabolism" commonly observed in inflammatory states. Cytokines also cause the release of reactive oxidants by immune cells resident in tissues in vivo. Therefore, we hypothesized that oxidative stress plays a role in the induction of hypermetabolism. We examined the effect of glucagon (1.0 nM), a catabolic stress hormone, and the oxidant H(2)O(2) (1.0 mM) on the metabolism of stable hepatocyte cultures for 4 days. Combined H(2)O(2) and glucagon treatment, but not H(2)O(2) or glucagon used alone, increased the hepatocyte oxygen uptake rate 25% above control untreated cells after a lag-time of 72 h. The same treatment also increased the expression of mitochondrial uncoupling protein-2 (UCP2). These effects were significantly inhibited by the antioxidant N-acetylcysteine (5mM) and the pentose phosphate pathway (PPP) inhibitor dehydroepianderosterone (200 microM). Glucagon alone induced urea synthesis and H(2)O(2) alone induced the PPP. These findings show, for the first time, that oxidative stress, in combination with glucagon, increases metabolic energy expenditure in cultured cells, and that this effect may be mediated by UCP-2. Furthermore, the results implicate the PPP in the induction of the hypermetabolic response.

journal_name

Metab Eng

journal_title

Metabolic engineering

authors

Lee K,Berthiaume F,Stephanopoulos GN,Yarmush ML

doi

10.1016/s1096-7176(03)00042-9

subject

Has Abstract

pub_date

2003-10-01 00:00:00

pages

221-9

issue

4

eissn

1096-7176

issn

1096-7184

pii

S1096717603000429

journal_volume

5

pub_type

杂志文章
  • Geobacter sulfurreducens strain engineered for increased rates of respiration.

    abstract::Geobacter species are among the most effective microorganisms known for the bioremediation of radioactive and toxic metals in contaminated subsurface environments and for converting organic compounds to electricity in microbial fuel cells. However, faster rates of electron transfer could aid in optimizing these proces...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2008.06.005

    authors: Izallalen M,Mahadevan R,Burgard A,Postier B,Didonato R Jr,Sun J,Schilling CH,Lovley DR

    更新日期:2008-09-01 00:00:00

  • An engineered E.coli strain for the production of glycoglycerolipids.

    abstract::The glycolipid synthase MG517 from Mycoplasma genitalium catalyzes the glucosyl transfer from UDPGlc to diacylglycerol producing glycoglycerolipids (GGL) (Andrés et al., 2011). The enzyme was functional in E. coli accumulating GGL in the plasma membrane. A metabolic engineering strategy for GGL production was evaluate...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2012.06.001

    authors: Mora-Buyé N,Faijes M,Planas A

    更新日期:2012-09-01 00:00:00

  • The organization of metabolic reaction networks. II. Signal processing in hierarchical structured functional units.

    abstract::Based on the analysis of molecular interactions of proteins with DNA binding sites, a new approach to developing mathematical models describing gene expression is introduced. Detection of hierarchical structures in metabolic networks can be used to decompose complex reaction schemes. This will be achieved by assigning...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1006/mben.2000.0175

    authors: Kremling A,Gilles ED

    更新日期:2001-04-01 00:00:00

  • Complete genome sequence, metabolic model construction and phenotypic characterization of Geobacillus LC300, an extremely thermophilic, fast growing, xylose-utilizing bacterium.

    abstract::We have isolated a new extremely thermophilic fast-growing Geobacillus strain that can efficiently utilize xylose, glucose, mannose and galactose for cell growth. When grown aerobically at 72 °C, Geobacillus LC300 has a growth rate of 2.15 h(-1) on glucose and 1.52 h(-1) on xylose (doubling time less than 30 min). The...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2015.09.009

    authors: Cordova LT,Long CP,Venkataramanan KP,Antoniewicz MR

    更新日期:2015-11-01 00:00:00

  • Improvement of 1,3-propanediol production using an engineered cyanobacterium, Synechococcus elongatus by optimization of the gene expression level of a synthetic metabolic pathway and production conditions.

    abstract::The introduction of a synthetic metabolic pathway consisting of multiple genes derived from various organisms enables cyanobacteria to directly produce valuable chemicals from carbon dioxide. We previously constructed a synthetic metabolic pathway composed of genes from Escherichia coli, Saccharomyces cerevisiae, and ...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2016.12.001

    authors: Hirokawa Y,Maki Y,Hanai T

    更新日期:2017-01-01 00:00:00

  • RCA-I-resistant CHO mutant cells have dysfunctional GnT I and expression of normal GnT I in these mutants enhances sialylation of recombinant erythropoietin.

    abstract::A large number of CHO glycosylation mutants were isolated by Ricinus communis agglutinin-I (RCA-I). Complementation tests revealed that all these mutant lines possessed a dysfunctional N-acetylglucosaminyltransferase I (GnT I) gene. Sequencing analyses on the GnT I cDNAs isolated from 16 mutant lines led to the identi...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2010.03.002

    authors: Goh JS,Zhang P,Chan KF,Lee MM,Lim SF,Song Z

    更新日期:2010-07-01 00:00:00

  • Reversal of β-oxidative pathways for the microbial production of chemicals and polymer building blocks.

    abstract::β-Oxidation is the ubiquitous metabolic strategy to break down fatty acids. In the course of this four-step process, two carbon atoms are liberated per cycle from the fatty acid chain in the form of acetyl-CoA. However, typical β-oxidative strategies are not restricted to monocarboxylic (fatty) acid degradation only, ...

    journal_title:Metabolic engineering

    pub_type: 杂志文章,评审

    doi:10.1016/j.ymben.2017.05.004

    authors: Kallscheuer N,Polen T,Bott M,Marienhagen J

    更新日期:2017-07-01 00:00:00

  • A real-time control system of gene expression using ligand-bound nucleic acid aptamer for metabolic engineering.

    abstract::Artificial control of bio-functions through regulating gene expression is one of the most important and attractive technologies to build novel living systems that are useful in the areas of chemical synthesis, nanotechnology, pharmacology, cell biology. Here, we present a novel real-time control system of gene regulat...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2017.06.002

    authors: Wang J,Cui X,Yang L,Zhang Z,Lv L,Wang H,Zhao Z,Guan N,Dong L,Chen R

    更新日期:2017-07-01 00:00:00

  • Metabolic engineering of fatty acid biosynthesis in plants.

    abstract::Fatty acids are the most abundant form of reduced carbon chains available from nature and have diverse uses ranging from food to industrial feedstocks. Plants represent a significant renewable source of fatty acids because many species accumulate them in the form of triacylglycerol as major storage components in seeds...

    journal_title:Metabolic engineering

    pub_type: 杂志文章,评审

    doi:10.1006/mben.2001.0204

    authors: Thelen JJ,Ohlrogge JB

    更新日期:2002-01-01 00:00:00

  • Escherichia coli responds with a rapid and large change in growth rate upon a shift from glucose-limited to glucose-excess conditions.

    abstract::Glucose pulse experiments at seconds time scale resolution were performed in aerobic glucose-limited Escherichia coli chemostat cultures. The dynamic responses of oxygen-uptake and growth rate at seconds time scale were determined using a new method based on the dynamic liquid-phase mass balance for oxygen and the pse...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2011.03.003

    authors: Taymaz-Nikerel H,van Gulik WM,Heijnen JJ

    更新日期:2011-05-01 00:00:00

  • Metabolic engineering of strains of Ralstonia eutropha and Pseudomonas putida for biotechnological production of 2-methylcitric acid.

    abstract::In this study strains of Ralstonia eutropha H16 and Pseudomonas putida KT2440 were engineered which are suitable for biotechnological production of 2-methylcitric acid (2MC). Analysis of a previous mutant of R. eutropha able to accumulate 2MC recommended this strain as a candidate for fermentative production of 2MC. T...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2006.05.007

    authors: Ewering C,Heuser F,Benölken JK,Brämer CO,Steinbüchel A

    更新日期:2006-11-01 00:00:00

  • Expanding the chemical palate of cells by combining systems biology and metabolic engineering.

    abstract::The field of Metabolic Engineering has recently undergone a transformation that has led to a rapid expansion of the chemical palate of cells. Now, it is conceivable to produce nearly any organic molecule of interest using a cellular host. Significant advances have been made in the production of biofuels, biopolymers a...

    journal_title:Metabolic engineering

    pub_type: 杂志文章,评审

    doi:10.1016/j.ymben.2012.04.006

    authors: Curran KA,Alper HS

    更新日期:2012-07-01 00:00:00

  • Functional genomics for the oleaginous yeast Yarrowia lipolytica.

    abstract::Oleaginous yeasts are valuable systems for biosustainable production of hydrocarbon-based chemicals. Yarrowia lipolytica is one of the best characterized of these yeast with respect to genome annotation and flux analysis of metabolic processes. Nonetheless, progress is hampered by a dearth of genome-wide tools enablin...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2018.05.008

    authors: Patterson K,Yu J,Landberg J,Chang I,Shavarebi F,Bilanchone V,Sandmeyer S

    更新日期:2018-07-01 00:00:00

  • Metabolic engineering of aerobic succinate production systems in Escherichia coli to improve process productivity and achieve the maximum theoretical succinate yield.

    abstract::The potential to produce succinate aerobically in Escherichia coli would offer great advantages over anaerobic fermentation in terms of faster biomass generation, carbon throughput, and product formation. Genetic manipulations were performed on two aerobic succinate production systems to increase their succinate yield...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2004.10.003

    authors: Lin H,Bennett GN,San KY

    更新日期:2005-03-01 00:00:00

  • Metabolic flux rearrangement in the amino acid metabolism reduces ammonia stress in the α1-antitrypsin producing human AGE1.HN cell line.

    abstract::This study focused on metabolic changes in the neuronal human cell line AGE1.HN upon increased ammonia stress. Batch cultivations of α(1)-antitrypsin (A1AT) producing AGE1.HN cells were carried out in media with initial ammonia concentrations ranging from 0mM to 5mM. Growth, A1AT production, metabolite dynamics and fi...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2012.01.001

    authors: Priesnitz C,Niklas J,Rose T,Sandig V,Heinzle E

    更新日期:2012-03-01 00:00:00

  • Punicic acid production in Brassica napus.

    abstract::Punicic acid (PuA; 18:3Δ9cis,11trans,13cis), a conjugated linolenic acid isomer bearing three conjugated double bonds, is associated with various health benefits and has potential for industrial use. The major nature source of this unusual fatty acid is pomegranate (Punica granatum) seed oil, which contains up to 80% ...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2020.08.011

    authors: Xu Y,Mietkiewska E,Shah S,Weselake RJ,Chen G

    更新日期:2020-11-01 00:00:00

  • Identification and elimination of metabolic bottlenecks in the quinone modification pathway for enhanced coenzyme Q10 production in Rhodobacter sphaeroides.

    abstract::In this report, UbiE and UbiH in the quinone modification pathway (QMP) were identified in addition to UbiG as bottleneck enzymes in the CoQ10 biosynthesis by Rhodobacter sphaeroides. The CoQ10 content was enhanced after co-overexpression of UbiE and UbiG, however, accompanied by the accumulation of the intermediate 1...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2015.03.012

    authors: Lu W,Ye L,Lv X,Xie W,Gu J,Chen Z,Zhu Y,Li A,Yu H

    更新日期:2015-05-01 00:00:00

  • Mapping photoautotrophic metabolism with isotopically nonstationary (13)C flux analysis.

    abstract::Understanding in vivo regulation of photoautotrophic metabolism is important for identifying strategies to improve photosynthetic efficiency or re-route carbon fluxes to desirable end products. We have developed an approach to reconstruct comprehensive flux maps of photoautotrophic metabolism by computational analysis...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2011.08.002

    authors: Young JD,Shastri AA,Stephanopoulos G,Morgan JA

    更新日期:2011-11-01 00:00:00

  • A metabolic network analysis & NMR experiment design tool with user interface-driven model construction for depth-first search analysis.

    abstract::A Windows program for metabolic engineering analysis and experimental design has been developed. A graphical user interface enables the pictorial, "on-screen" construction of a metabolic network. Once a model is composed, balance equations are automatically generated. Model construction, modification and information e...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/s1096-7176(03)00023-5

    authors: Zhu T,Phalakornkule C,Ghosh S,Grossmann IE,Koepsel RR,Ataai MM,Domach MM

    更新日期:2003-04-01 00:00:00

  • 13C metabolic flux analysis of microbial and mammalian systems is enhanced with GC-MS measurements of glycogen and RNA labeling.

    abstract::13C metabolic flux analysis (13C-MFA) is a widely used tool for quantitative analysis of microbial and mammalian metabolism. Until now, 13C-MFA was based mainly on measurements of isotopic labeling of amino acids derived from hydrolyzed biomass proteins and isotopic labeling of extracted intracellular metabolites. Her...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2016.06.007

    authors: Long CP,Au J,Gonzalez JE,Antoniewicz MR

    更新日期:2016-11-01 00:00:00

  • Glycosylation flux analysis reveals dynamic changes of intracellular glycosylation flux distribution in Chinese hamster ovary fed-batch cultures.

    abstract::N-linked glycosylation of proteins has both functional and structural significance. Importantly, the glycan structure of a therapeutic protein influences its efficacy, pharmacokinetics, pharmacodynamics and immunogenicity. In this work, we developed glycosylation flux analysis (GFA) for predicting intracellular produc...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2017.07.005

    authors: Hutter S,Villiger TK,Brühlmann D,Stettler M,Broly H,Soos M,Gunawan R

    更新日期:2017-09-01 00:00:00

  • Identification of Absidia orchidis steroid 11β-hydroxylation system and its application in engineering Saccharomyces cerevisiae for one-step biotransformation to produce hydrocortisone.

    abstract::Hydrocortisone is an effective anti-inflammatory drug and also an important intermediate for synthesis of other steroid drugs. The filamentous fungus Absidia orchidis is renowned for biotransformation of acetylated cortexolone through 11β-hydroxylation to produce hydrocortisone. However, due to the presence of 11α-hyd...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2019.10.006

    authors: Chen J,Fan F,Qu G,Tang J,Xi Y,Bi C,Sun Z,Zhang X

    更新日期:2020-01-01 00:00:00

  • Metabolic fluxes and metabolic engineering.

    abstract::Metabolic engineering is the directed improvement of cellular properties through the modification of specific biochemical reactions or the introduction of new ones, with the use of recombinant DNA technology. As such, metabolic engineering emphasizes metabolic pathway integration and relies on metabolic fluxes as dete...

    journal_title:Metabolic engineering

    pub_type: 杂志文章,评审

    doi:10.1006/mben.1998.0101

    authors: Stephanopoulos G

    更新日期:1999-01-01 00:00:00

  • Anaerobic production of medium-chain fatty alcohols via a β-reduction pathway.

    abstract::In this report, we identify the relevant factors to increase production of medium chain n-alcohols through an expanded view of the reverse β-oxidation pathway. We began by creating a base strain capable of producing medium chain n-alcohols from glucose using a redox-balanced and growth-coupled metabolic engineering st...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2018.05.011

    authors: Mehrer CR,Incha MR,Politz MC,Pfleger BF

    更新日期:2018-07-01 00:00:00

  • Production of muconic acid in plants.

    abstract::Muconic acid (MA) is a dicarboxylic acid used for the production of industrially relevant chemicals such as adipic acid, terephthalic acid, and caprolactam. Because the synthesis of these polymer precursors generates toxic intermediates by utilizing petroleum-derived chemicals and corrosive catalysts, the development ...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2018.02.002

    authors: Eudes A,Berthomieu R,Hao Z,Zhao N,Benites VT,Baidoo EEK,Loqué D

    更新日期:2018-03-01 00:00:00

  • Bio-based succinate from sucrose: High-resolution 13C metabolic flux analysis and metabolic engineering of the rumen bacterium Basfia succiniciproducens.

    abstract::Succinic acid is a platform chemical of recognized industrial value and accordingly faces a continuous challenge to enable manufacturing from most attractive raw materials. It is mainly produced from glucose, using microbial fermentation. Here, we explore and optimize succinate production from sucrose, a globally appl...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2017.10.003

    authors: Lange A,Becker J,Schulze D,Cahoreau E,Portais JC,Haefner S,Schröder H,Krawczyk J,Zelder O,Wittmann C

    更新日期:2017-11-01 00:00:00

  • Introduction of a bacterial acetyl-CoA synthesis pathway improves lactic acid production in Saccharomyces cerevisiae.

    abstract::Acid-tolerant Saccharomyces cerevisiae was engineered to produce lactic acid by expressing heterologous lactate dehydrogenase (LDH) genes, while attenuating several key pathway genes, including glycerol-3-phosphate dehydrogenase1 (GPD1) and cytochrome-c oxidoreductase2 (CYB2). In order to increase the yield of lactic ...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2015.09.006

    authors: Song JY,Park JS,Kang CD,Cho HY,Yang D,Lee S,Cho KM

    更新日期:2016-05-01 00:00:00

  • Novel chemobiosynthetic approach for exclusive production of FK506.

    abstract::FK506, a widely used immunosuppressant, is produced by industrial fermentation processes using various Streptomyces species. Independently of the strain, structurally related compound FK520 is co-produced, resulting in complex and costly isolation procedures. In this paper, we report a chemobiosynthetic approach for e...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2011.11.003

    authors: Kosec G,Goranovič D,Mrak P,Fujs S,Kuščer E,Horvat J,Kopitar G,Petković H

    更新日期:2012-01-01 00:00:00

  • Step changes in leaf oil accumulation via iterative metabolic engineering.

    abstract::Synthesis and accumulation of plant oils in the entire vegetative biomass offers the potential to deliver yields surpassing those of oilseed crops. However, current levels still fall well short of those typically found in oilseeds. Here we show how transcriptome and biochemical analyses pointed to a futile cycle in a ...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2016.12.007

    authors: Vanhercke T,Divi UK,El Tahchy A,Liu Q,Mitchell M,Taylor MC,Eastmond PJ,Bryant F,Mechanicos A,Blundell C,Zhi Y,Belide S,Shrestha P,Zhou XR,Ral JP,White RG,Green A,Singh SP,Petrie JR

    更新日期:2017-01-01 00:00:00

  • Coupled incremental precursor and co-factor supply improves 3-hydroxypropionic acid production in Saccharomyces cerevisiae.

    abstract::3-Hydroxypropionic acid (3-HP) is an attractive platform chemical, which can be used to produce a variety of commodity chemicals, such as acrylic acid and acrylamide. For enabling a sustainable alternative to petrochemicals as the feedstock for these commercially important chemicals, fermentative production of 3-HP is...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2014.01.005

    authors: Chen Y,Bao J,Kim IK,Siewers V,Nielsen J

    更新日期:2014-03-01 00:00:00