Liver proteomic response to hypertriglyceridemia in human-apolipoprotein C-III transgenic mice at cellular and mitochondrial compartment levels

Ehx, Grégory; Gerin, Stéphanie; Mathy, Grégory; Franck, Fabrice; Oliveira, Helena CF; Vercesi, Anibal E; Sluse, Francis

doi:10.1186/1476-511X-13-116

Article (Scientific journals)

Liver proteomic response to hypertriglyceridemia in human-apolipoprotein C-III transgenic mice at cellular and mitochondrial compartment levels

Ehx, Grégory; Gerin, Stéphanie; Mathy, Grégory et al.

2014 • In Lipids in Health and Disease, 13, p. 116

Peer Reviewed verified by ORBi

Permalink
https://hdl.handle.net/2268/170861

DOI
10.1186/1476-511X-13-116

PubMed
25047818

Files (1)Send to Details Statistics Bibliography Similar publications

Files

Full Text

Ehx G & Gérin S - Liver proteomic response to HTG in HuApoC-III mice.pdf

Publisher postprint (1.82 MB)

Download

All documents in ORBi are protected by a user license.

Send to

RIS BibTex APA Chicago Permalink X Linkedin

Details

Abstract :

[en] Background: Hypertriglyceridemia (HTG) is defined as a triglyceride (TG) plasma level exceeding 150 mg/dl and is tightly associated with atherosclerosis, metabolic syndrome, obesity, diabetes and acute pancreatitis. The present study was undertaken to investigate the impact of hypertriglyceridemia on the mitochondrial, sub-mitochondrial and cellular proteomes in the hepatocytes of a hypertriglyceridemic transgenic mouse model overexpressing the human apolipoproteinC-III. Methods: Quantitative comparative proteomics (2D-DIGE) was carried out in both “low-expressor” (LE) and “high-expressor” (HE) mice, respectively exhibiting moderate and severe HTG, to characterize the effect of the TG plasma level on the proteomic response. Results: The mitoproteome analysis revealed the occurrence of a large-scale adaptation in transgenic mice consisting of a general down-regulation of matricial proteins and up-regulation of inner membrane proteins. Remarkably, the magnitude of these proteomic changes appears to strongly depend on the TG plasma level. Altogether, our different analyses indicate that, in HE mice, the capacity of several metabolic pathways is altered to promote the availability of acetyl-CoA, glycerol-3-phosphate, ATP and NADPH for de novo TG biosynthesis. The up-regulation of several cytosolic ROS detoxifying enzymes also tend to confirm that the cytoplasm of HTG mice is subjected to oxidative stress as previously stated. The up-regulation of cytosolic ferritin indicates that iron over-accumulation could take place in the cytosol of HE mice hepatocytes and contribute to (i) enhance oxidative stress and (ii) promote cellular proliferation. Conclusions: The present analyses demonstrate that important TG dose-responsive metabolic adaptations are set up in human apolipoproteinC-III-overexpressing mice. Our results indicate that these adaptations could support the higher TG production rates which have been previously reported in this HTG model, and also suggest that cytosolic oxidative stress may result from FFA over-accumulation, iron overload and enhanced activity of some ROS-producing catabolic enzymes.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Ehx, Grégory ^✱; Université de Liège - ULiège > GIGA-R : Hématologie

Gerin, Stéphanie ^✱; Université de Liège - ULiège > Labo de Bioénergétique

Mathy, Grégory

Franck, Fabrice ; Université de Liège - ULiège > Labo de Bioénergétique

Oliveira, Helena CF

Vercesi, Anibal E

Sluse, Francis ; Université de Liège - ULiège > Département des sciences de la vie > Département des sciences de la vie

^✱ These authors have contributed equally to this work.

Language :

English

Title :

Liver proteomic response to hypertriglyceridemia in human-apolipoprotein C-III transgenic mice at cellular and mitochondrial compartment levels

Publication date :

21 July 2014

Journal title :

Lipids in Health and Disease

eISSN :

1476-511X

Publisher :

BioMed Central, United Kingdom

Volume :

Pages :

116

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

http://www.lipidworld.com/content/13/1/116/abstract

Funders :

FRFC - Fonds de la Recherche Fondamentale Collective

Available on ORBi :

since 27 July 2014

Statistics

Number of views

131 (21 by ULiège)

Number of downloads

209 (2 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

Bibliography

Definition of metabolic syndrome: report of the national heart, lung, and blood institute/american heart association conference on scientific issues related to definition. Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C, Circulation 2004 109 433 438 (Pubitemid 38133916)
Nonalcoholic steatohepatitis. Reid AE, Gastroenterology 2001 121 710 723 (Pubitemid 32822586)
Hyperlipidemic pancreatitis. Toskes PP, Gastroenterol Clin North Am 1990 19 783 791
Apolipoprotein B metabolism in subjects with deficiency of apolipoproteins CIII and AI. Evidence that apolipoprotein CIII inhibits catabolism of triglyceride-rich lipoproteins by lipoprotein lipase in vivo. Ginsberg HN, Le NA, Goldberg IJ, Gibson JC, Rubinstein A, Wang-Iverson P, Norum R, Brown WV, J Clin Invest 1986 78 1287 1295 (Pubitemid 17181567)
Targeted disruption of the apolipoprotein C-III gene in mice results in hypotriglyceridemia and protection from postprandial hypertriglyceridemia. Maeda N, Li H, Lee D, Oliver P, Quarfordt SH, Osada J, J Biol Chem 1994 269 23610 23616 (Pubitemid 24293564)
Variation at the apo AI/CIII/AIV gene complex is associated with elevated plasma levels of apo CIII. Shoulders CC, Harry PJ, Lagrost L, White SE, Shah NF, North JD, Gilligan M, Gambert P, Ball MJ, Atherosclerosis 1991 87 239 247
Apolipoprotein C-III deficiency accelerates triglyceride hydrolysis by lipoprotein lipase in wild-type and apoE knockout mice. Jong MC, Rensen PC, Dahlmans VE, van der Boom H, van Berkel TJ, Havekes LM, J Lipid Res 2001 42 1578 1585 (Pubitemid 33026056)
Modulation of lipoprotein lipase activity by apolipoproteins. Effect of apolipoprotein C-III. Wang CS, McConathy WJ, Kloer HU, Alaupovic P, J Clin Invest 1985 75 384 390 (Pubitemid 15143476)
Inhibitory effects of specific apolipoprotein C-III isoforms on the binding of triglyceride-rich lipoproteins to the lipolysis-stimulated receptor. Mann CJ, Troussard AA, Yen FT, Hannouche N, Najib J, Fruchart JC, Lotteau V, Andre P, Bihain BE, J Biol Chem 1997 272 31348 31354 (Pubitemid 28013269)
Inhibitory effects of C apolipoproteins from rats and humans on the uptake of triglyceride-rich lipoproteins and their remnants by the perfused rat liver. Windler E, Havel RJ, J Lipid Res 1985 26 556 565 (Pubitemid 15073727)
Hypertriglyceridemia as a result of human apo CIII gene expression in transgenic mice. Ito Y, Azrolan N, O'Connell A, Walsh A, Breslow JL, Science 1990 249 790 793
Mechanism of hypertriglyceridemia in human apolipoprotein (apo) CIII transgenic mice. Diminished very low density lipoprotein fractional catabolic rate associated with increased apo CIII and reduced apo E on the particles. Aalto-Setala K, Fisher EA, Chen X, Chajek-Shaul T, Hayek T, Zechner R, Walsh A, Ramakrishnan R, Ginsberg HN, Breslow JL, J Clin Invest 1992 90 1889 1900
Hypertriglyceridemic mice transgenic for the human apolipoprotein C-III gene are neither insulin resistant nor hyperinsulinemic. Reaven GM, Mondon CE, Chen YD, Breslow JL, J Lipid Res 1994 35 820 824 (Pubitemid 24157233)
Hyperlipidemic mice present enhanced catabolism and higher mitochondrial ATP-sensitive K + channel activity. Alberici LC, Oliveira HC, Patricio PR, Kowaltowski AJ, Vercesi AE, Gastroenterology 2006 131 1228 1234 (Pubitemid 44498696)
Overexpression of apolipoprotein CIII increases and CETP reverses diet-induced obesity in transgenic mice. Salerno AG, Silva TR, Amaral ME, Alberici LC, Bonfleur ML, Patricio PR, Francesconi EP, Grassi-Kassisse DM, Vercesi AE, Boschero AC, Oliveira HC, Int J Obes (Lond) 2007 31 1586 1595 (Pubitemid 47482661)
Plasma glucose regulation and insulin secretion in hypertriglyceridemic mice. Amaral ME, Oliveira HC, Carneiro EM, Delghingaro-Augusto V, Vieira EC, Berti JA, Boschero AC, Horm Metab Res 2002 34 21 26 (Pubitemid 34135466)
Mitochondrial energy metabolism and redox responses to hypertriglyceridemia. Alberici LC, Vercesi AE, Oliveira HC, J Bioenerg Biomembr 2011 43 19 23
Hypertriglyceridemia increases mitochondrial resting respiration and susceptibility to permeability transition. Alberici LC, Oliveira HC, Bighetti EJ, de Faria EC, Degaspari GR, Souza CT, Vercesi AE, J Bioenerg Biomembr 2003 35 451 457 (Pubitemid 37517874)
Mitochondrial potassium transport: the K(+) cycle. Garlid KD, Paucek P, Biochim Biophys Acta 2003 1606 23 41
Mitochondrial ATP-sensitive K(+) channels as redox signals to liver mitochondria in response to hypertriglyceridemia. Alberici LC, Oliveira HC, Paim BA, Mantello CC, Augusto AC, Zecchin KG, Gurgueira SA, Kowaltowski AJ, Vercesi AE, Free Radic Biol Med 2009 47 1432 1439
Mitochondrial comparative proteomics: strengths and pitfalls. Mathy G, Sluse FE, Biochim Biophys Acta 2008 1777 1072 1077
Steatosis-induced proteomic changes in liver mitochondria evidenced by two-dimensional differential in-gel electrophoresis. Douette P, Navet R, Gerkens P, de Pauw E, Leprince P, Sluse-Goffart C, Sluse FE, J Proteome Res 2005 4 2024 2031 (Pubitemid 41814268)
The development of the DIGE system: 2D fluorescence difference gel analysis technology. Marouga R, David S, Hawkins E, Anal Bioanal Chem 2005 382 669 678 (Pubitemid 40890994)
Peroxiredoxins: a historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling. Rhee SG, Chae HZ, Kim K, Free Radic Biol Med 2005 38 1543 1552 (Pubitemid 40726061)
Glutathione transferases. Hayes JD, Flanagan JU, Jowsey IR, Annu Rev Pharmacol Toxicol 2005 45 51 88 (Pubitemid 40261798)
Carbonic anhydrase III protects cells from hydrogen peroxide-induced apoptosis. Raisanen SR, Lehenkari P, Tasanen M, Rahkila P, Harkonen PL, Vaananen HK, FASEB J 1999 13 513 522 (Pubitemid 29115569)
NDRG2 inhibits hepatocellular carcinoma adhesion, migration and invasion by regulating CD24 expression. Zheng J, Li Y, Yang J, Liu Q, Shi M, Zhang R, Shi H, Ren Q, Ma J, Guo H, Tao Y, Xue Y, Jiang N, Yao L, Liu W, BMC Cancer 2011 11 251 251 259
Apolipoprotein CIII overexpressing mice are predisposed to diet-induced hepatic steatosis and hepatic insulin resistance. Lee HY, Birkenfeld AL, Jornayvaz FR, Jurczak MJ, Kanda S, Popov V, Frederick DW, Zhang D, Guigni B, Bharadwaj KG, Choi CS, Goldberg IJ, Park JH, Petersen KF, Samuel VT, Shulman GI, Hepatology 2011 54 1650 1660
Saccharomyces cerevisiae mitoproteome plasticity in response to recombinant alternative ubiquinol oxidase. Mathy G, Navet R, Gerkens P, Leprince P, De Pauw E, Sluse-Goffart CM, Sluse FE, Douette P, J Proteome Res 2006 5 339 348 (Pubitemid 43222302)
Multiplex proteomic analysis by two-dimensional differential in-gel electrophoresis. Knowles MR, Cervino S, Skynner HA, Hunt SP, de Felipe C, Salim K, Meneses-Lorente G, McAllister G, Guest PC, Proteomics 2003 3 1162 1171 (Pubitemid 36929538)
Mitochondrial ion transport pathways: role in metabolic diseases. Cardoso AR, Queliconi BB, Kowaltowski AJ, Biochim Biophys Acta 2010 1797 832 838
Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice. Bonnard C, Durand A, Peyrol S, Chanseaume E, Chauvin MA, Morio B, Vidal H, Rieusset J, J Clin Invest 2008 118 789 800 (Pubitemid 351206566)
Evaluating and responding to mitochondrial dysfunction: the mitochondrial unfolded-protein response and beyond. Haynes CM, Fiorese CJ, Lin YF, Trends Cell Biol 2013 23 311 318
Activation of mitochondrial biogenesis by heme oxygenase-1-mediated NF-E2-related factor-2 induction rescues mice from lethal Staphylococcus aureus sepsis. MacGarvey NC, Suliman HB, Bartz RR, Fu P, Withers CM, Welty-Wolf KE, Piantadosi CA, Am J Respir Crit Care Med 2012 185 851 861
Sulforaphane protects ischemic injury of hearts through antioxidant pathway and mitochondrial K(ATP) channels. Piao CS, Gao S, Lee GH, Kim Do S, Park BH, Chae SW, Chae HJ, Kim SH, Pharmacol Res 2010 61 342 348
Statistical challenges in the analysis of two-dimensional difference gel electrophoresis experiments using DeCyder. Fodor IK, Nelson DO, Alegria-Hartman M, Robbins K, Langlois RG, Turteltaub KW, Corzett TH, McCutchen-Maloney SL, Bioinformatics 2005 21 3733 3740 (Pubitemid 41535521)
Normalization approaches for removing systematic biases associated with mass spectrometry and label-free proteomics. Callister SJ, Barry RC, Adkins JN, Johnson ET, Qian WJ, Webb-Robertson BJ, Smith RD, Lipton MS, J Proteome Res 2006 5 277 286 (Pubitemid 43222296)
Hypertriglyceridemia in lecithin-cholesterol acyltransferase-deficient mice is associated with hepatic overproduction of triglycerides, increased lipogenesis, and improved glucose tolerance. Ng DS, Xie C, Maguire GF, Zhu X, Ugwu F, Lam E, Connelly PW, J Biol Chem 2004 279 7636 7642 (Pubitemid 38294644)
Early hepatic insulin resistance in mice: a metabolomics analysis. Li LO, Hu YF, Wang L, Mitchell M, Berger A, Coleman RA, Mol Endocrinol 2010 24 657 666
Early changes in the liver-soluble proteome from mice fed a nonalcoholic steatohepatitis inducing diet. Thomas A, Stevens AP, Klein MS, Hellerbrand C, Dettmer K, Gronwald W, Oefner PJ, Reinders J, Proteomics 2012 12 1437 1451
Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Ray PD, Huang BW, Tsuji Y, Cell Signal 2012 24 981 990
The peroxisome in oxidative stress. Dansen TB, Wirtz KW, IUBMB Life 2001 51 223 230 (Pubitemid 32848153)
CYP2E1 and CYP4A as microsomal catalysts of lipid peroxides in murine nonalcoholic steatohepatitis. Leclercq IA, Farrell GC, Field J, Bell DR, Gonzalez FJ, Robertson GR, J Clin Invest 2000 105 1067 1075 (Pubitemid 30217691)
Genetic activation of Nrf2 protects against fasting-induced oxidative stress in livers of mice. Zhang YK, Wu KC, Klaassen CD, PLoS One 2013 8 59122
Intracellular iron transport and storage: from molecular mechanisms to health implications. MacKenzie EL, Iwasaki K, Tsuji Y, Antioxid Redox Signal 2008 10 997 1030 (Pubitemid 351451707)
Iron in fatty liver and in the metabolic syndrome: a promising therapeutic target. Dongiovanni P, Fracanzani AL, Fargion S, Valenti L, J Hepatol 2011 55 920 932
Binding of a cytosolic protein to the iron-responsive element of human ferritin messenger RNA. Rouault TA, Hentze MW, Caughman SW, Harford JB, Klausner RD, Science 1988 241 1207 1210
Identification of the iron-responsive element for the translational regulation of human ferritin mRNA. Hentze MW, Caughman SW, Rouault TA, Barriocanal JG, Dancis A, Harford JB, Klausner RD, Science 1987 238 1570 1573 (Pubitemid 18032473)
Proteomic analysis of hepatic iron overload in mice suggests dysregulation of urea cycle, impairment of fatty acid oxidation, and changes in the methylation cycle. Petrak J, Myslivcova D, Man P, Cmejla R, Cmejlova J, Vyoral D, Elleder M, Vulpe CD, Am J Physiol Gastrointest Liver Physiol 2007 292 1490 G1498
Nonalcoholic fatty liver disease. Krawczyk M, Bonfrate L, Portincasa P, Best Pract Res Clin Gastroenterol 2010 24 695 708
The role of oxidative stress in non-alcoholic steatohepatitis. Koek GH, Liedorp PR, Bast A, Clin Chim Acta 2011 412 1297 1305
Intramitochondrial crystalline inclusions in nonalcoholic steatohepatitis. Caldwell SH, de Freitas LA, Park SH, Moreno ML, Redick JA, Davis CA, Sisson BJ, Patrie JT, Cotrim H, Argo CK, Al-Osaimi A, Hepatology 2009 49 1888 1895
The proteome of Saccharomyces cerevisiae mitochondria. Sickmann A, Reinders J, Wagner Y, Joppich C, Zahedi R, Meyer HE, Schonfisch B, Perschil I, Chacinska A, Guiard B, Rehling P, Pfanner N, Meisinger C, Proc Natl Acad Sci U S A 2003 100 13207 13212 (Pubitemid 37444720)
An electron-transport system associated with the outer membrane of liver mitochondria. A biochemical and morphological study. Sottocasa GL, Kuylenstierna B, Ernster L, Bergstrand A, J Cell Biol 1967 32 415 438
Solubilization of plant membrane proteins for analysis by two-dimensional gel electrophoresis. Hurkman WJ, Tanaka CK, Plant Physiol 1986 81 802 806
A strategy for identifying gel-separated proteins in sequence databases by MS alone. Shevchenko A, Wilm M, Vorm O, Jensen ON, Podtelejnikov AV, Neubauer G, Shevchenko A, Mortensen P, Mann M, Biochem Soc Trans 1996 24 893 896 (Pubitemid 26306321)