siRNA screening identifies the host hexokinase 2 (HK2) gene as an important hypoxia-inducible transcription factor 1 (HIF-1) target gene in Toxoplasma gondii-infected cells

mBio

Volumn 6, Issue 3, 2015, Pages

  Menendez, Matthew T ^a,b   Teygong, Crystal ^a   Wade, Kristin ^a   Florimond, Celia ^b   Blader, Ira J ^b  

^a UNIVERSITY OF OKLAHOMA COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY AT BUFFALO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HYPOXIA INDUCIBLE FACTOR 1; LACTIC ACID; OXYGEN; SMALL INTERFERING RNA; HEXOKINASE; HIF1A PROTEIN, HUMAN; HYPOXIA INDUCIBLE FACTOR 1ALPHA;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; C2C12 CELL LINE; CONTROLLED STUDY; CYTOPLASM; FIBROBLAST; FLUORESCENCE MICROSCOPY; GENE; GENE EXPRESSION; GENE IDENTIFICATION; GLYCOLYSIS; HELA CELL LINE; HEXOKINASE 2 GENE; HUMAN; HUMAN CELL; LIVER; LUNG; MICROBIAL GROWTH; MITOCHONDRIAL MEMBRANE; MONOCYTE; MOUSE; MYOBLAST; NONHUMAN; NUCLEIC ACID ANALYSIS; OXYGEN TENSION; PLASMID; PRIORITY JOURNAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SPLEEN; TOXOPLASMA GONDII; TOXOPLASMOSIS; WESTERN BLOTTING; ANIMAL; ANIMAL TOXOPLASMOSIS; C57BL MOUSE; DRUG EFFECTS; ENZYMOLOGY; GENE EXPRESSION REGULATION; GENETIC SCREENING; GENETICS; HOST PATHOGEN INTERACTION; METABOLIC FLUX ANALYSIS; METABOLISM; PATHOLOGY; PHYSIOLOGY; TOXOPLASMA;

PROTOZOA; TOXOPLASMA; TOXOPLASMA GONDII;

ANIMALS; GENE EXPRESSION REGULATION; GENETIC TESTING; GLYCOLYSIS; HELA CELLS; HEXOKINASE; HOST-PATHOGEN INTERACTIONS; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; METABOLIC FLUX ANALYSIS; MICE, INBRED C57BL; MONOCYTES; RNA, SMALL INTERFERING; TOXOPLASMA; TOXOPLASMOSIS, ANIMAL;

EID: 84936976538     PISSN: 21612129     EISSN: 21507511     Source Type: Journal    
DOI: 10.1128/mBio.00462-15     Document Type: Article

References (54)

1. Ratcliffe PJ. 2013. Oxygen sensing and hypoxia signalling pathways in animals: the implications of physiology for cancer. J Physiol 591: 2027-2042. http://dx.doi.org/10.1113/jphysiol.2013.251470.
2. Bruick RK, McKnight SL. 2001. A conserved family of prolyl-4-hydroxylases that modify HIF. Science 294:1337-1340. http://dx.doi.org/ 10.1126/science.1066373.
3. Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM, Lane WS, Kaelin WG, Jr. 2001. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications forO2 sensing. Science 292:464-468. http://dx.doi.org/10.1126/science.1059817.
4. Mathupala SP, Rempel A, Pedersen PL. 2001. Glucose catabolism in cancer cells: identification and characterization of a marked activation response of the type II hexokinase gene to hypoxic conditions. J Biol Chem 276:43407-43412. http://dx.doi.org/10.1074/jbc.M108181200.
5. Wolf A, Agnihotri S, Micallef J, Mukherjee J, Sabha N, Cairns R, Hawkins C, Guha A. 2011. Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme. J Exp Med 208:313-326. http://dx.doi.org/10.1084/jem.20101470.
6. Koppenol WH, Bounds PL, Dang CV. 2011. Otto Warburg's contributions to current concepts of cancer metabolism. Nat Rev Cancer 11: 325-337. http://dx.doi.org/10.1038/nrc3038.
7. Galván-Peña S, O'Neill LA. 2014. Metabolic reprograming in macrophage polarization. Front Immunol 5:420. http://dx.doi.org/10.3389/ fimmu.2014.00420.
8. Xie GC, Wilson JE. 1988. Rat brain hexokinase: the hydrophobic N-terminus of the mitochondrially bound enzyme is inserted in the lipid bilayer. Arch Biochem Biophys 267:803-810. http://dx.doi.org/10.1016/ 0003-9861(88)90090-2.
9. Abu-Hamad S, Zaid H, Israelson A, Nahon E, Shoshan-Barmatz V. 2008. Hexokinase-I protection against apoptotic cell death is mediated via interaction with the voltage-dependent anion channel-1: mapping the site of binding. J Biol Chem 283:13482-13490. http://dx.doi.org/10.1074/ jbc.M708216200.
10. Arzoine L, Zilberberg N, Ben-Romano R, Shoshan-Barmatz V. 2009. Voltage-dependent anion channel 1-based peptides interact with hexokinase to prevent its anti-apoptotic activity. J Biol Chem 284:3946-3955. http://dx.doi.org/10.1074/jbc.M803614200.
11. John S, Weiss JN, Ribalet B. 2011. Subcellular localization of hexokinases I and II directs the metabolic fate of glucose. PLoS One 6:e17674. http:// dx.doi.org/10.1371/journal.pone.0017674.
12. BeltrandelRio H, Wilson JE. 1992. Coordinated regulation of cerebral glycolytic and oxidative metabolism, mediated by mitochondrially bound hexokinase dependent on intramitochondrially generated ATP. Arch Biochem Biophys 296:667-677. http://dx.doi.org/10.1016/0003-9861(92)90625-7.
13. Kim K, Weiss LM. 2004. Toxoplasma gondii: the model apicomplexan. Int J Parasitol 34:423-432. http://dx.doi.org/10.1016/j.ijpara.2003.12.009.
14. Munoz M, Liesenfeld O, Heimesaat MM. 2011. Immunology of Toxoplasma gondii. Immunol Rev 240:269-285. http://dx.doi.org/10.1111/ j.1600-065X.2010.00992.x.
15. Blader IJ, Manger ID, Boothroyd JC. 2001. Microarray analysis reveals previously unknown changes in Toxoplasma gondii-infected human cells. J Biol Chem 276:24223-24231. http://dx.doi.org/10.1074/ jbc.M100951200.
16. Spear W, Chan D, Coppens I, Johnson RS, Giaccia A, Blader IJ. 2006. The host cell transcription factor hypoxia-inducible factor 1 is required for Toxoplasma gondii growth and survival at physiological oxygen levels. Cell Microbiol 8 :339-352. http://dx.doi.org/10.1111/j.1462-5822.2005.00628.x
17. Gaji RY, Huynh MH, Carruthers VB. 2013. A novel high throughput invasion screen identifies host actin regulators required for efficient cell entry by Toxoplasma gondii. PLoS One 8:e64693. http://dx.doi.org/ 10.1371/journal.pone.0064693.
18. Krajewska M, Kim H, Shin E, Kennedy S, Duffy MJ, Wong YF, Marr D, Mikolajczyk J, Shabaik A, Meinhold-Heerlein I, Huang X, Banares S, Hedayat H, Reed JC, Krajewski S. 2005. Tumor-associated alterations in caspase-14 expression in epithelial malignancies. Clin Cancer Res 11: 5462-5471. http://dx.doi.org/10.1158/1078-0432.CCR-04-2527.
19. Weilhammer DR, Iavarone AT, Villegas EN, Brooks GA, Sinai AP, Sha WC. 2012. Host metabolism regulates growth and differentiation of Toxoplasma gondii. Int J Parasitol 42:947-959. http://dx.doi.org/10.1016/ j.ijpara.2012.07.011.
20. Ullah MS, Davies AJ, Halestrap AP. 2006. The plasma membrane lactate transporter MCT4, but not MCT1, is up-regulated by hypoxia through a HIF-1alpha-dependent mechanism. J Biol Chem 281:9030-9037. http:// dx.doi.org/10.1074/jbc.M511397200.
21. Patel MS, Korotchkina LG. 2006. Regulation of the pyruvate dehydrogenase complex. Biochem Soc Trans 34:217-222. http://dx.doi.org/10.1042/ BST20060217.
22. Ryan HE, Lo J, Johnson RS. 1998. HIF-1alpha is required for solid tumor formation and embryonic vascularization. EMBO J 17:3005-3015. http:// dx.doi.org/10.1093/emboj/17.11.3005.
23. Swierzy IJ, Lüder CG. 2015. Withdrawal of skeletal muscle cells from cell cycle progression triggers differentiation of Toxoplasma gondii towards the bradyzoite stage. Cell Microbiol 17:2-17. http://dx.doi.org/10.1111/ cmi.12342.
24. Yaffe D, Saxel O. 1977. Serial passaging and differentiation of myogenic cells isolated from dystrophic mouse muscle. Nature 270:725-727. http:// dx.doi.org/10.1038/270725a0.
25. Hitziger N, Dellacasa I, Albiger B, Barragan A. 2005. Dissemination of Toxoplasma gondii to immunoprivileged organs and role of toll/ interleukin-1 receptor signalling for host resistance assessed by in vivo bioluminescence imaging. Cell Microbiol 7:837-848. http://dx.doi.org/ 10.1111/j.1462-5822.2005.00517.x.
26. Fentress SJ, Behnke MS, Dunay IR, Mashayekhi M, Rommereim LM, Fox BA, Bzik DJ, Taylor GA, Turk BE, Lichti CF, Townsend RR, Qiu W, Hui R, Beatty WL, Sibley LD. 2010. Phosphorylation of immunityrelated GTPases by a Toxoplasma gondii-secreted kinase promotes macrophage survival and virulence. Cell Host Microbe 8:484-495. http:// dx.doi.org/10.1016/j.chom.2010.11.005.
27. Ardehali H, Yano Y, Printz RL, Koch S, Whitesell RR, May JM, Granner DK. 1996. Functional organization of mammalian hexokinase II: retention of catalytic and regulatory functions in both the NH-and COOHterminal halves. J Biol Chem 271:1849-1852.
28. Cheung EC, Ludwig RL, Vousden KH. 2012. Mitochondrial localization of TIGAR under hypoxia stimulates HK2 and lowers ROS and cell death. Proc Natl Acad Sci U S A 109:20491-20496. http://dx.doi.org/10.1073/ pnas.1206530109.
29. Geisler S, Vollmer S, Golombek S, Kahle PJ. 2014. The ubiquitinconjugating enzymes UBE2N, UBE2L3 and UBE2D2/3 are essential for Parkin-dependent mitophagy. J Cell Sci 127:3280-3293. http:// dx.doi.org/10.1242/jcs.146035.
30. Wiley M, Sweeney KR, Chan DA, Brown KM, McMurtrey C, Howard EW, Giaccia AJ, Blader IJ. 2010. Toxoplasma gondii activates hypoxia inducible factor by stabilizing the HIF-1alpha subunit via type I activin like receptor kinase receptor signaling. J Biol Chem 285:26852-26860. http://dx.doi.org/10.1074/jbc.M110.147785.
31. Jackson AL, Bartz SR, Schelter J, Kobayashi SV, Burchard J, Mao M, Li B, Cavet G, Linsley PS. 2003. Expression profiling reveals off-target gene regulation by RNAi. Nat Biotechnol 21:635-637. http://dx.doi.org/ 10.1038/nbt831.
32. Bougdour A, Durandau E, Brenier-Pinchart MP, Ortet P, Barakat M, Kieffer S, Curt-Varesano A, Curt-Bertini RL, Bastien O, Coute Y, Pelloux H, Hakimi MA. 2013. Host cell subversion by Toxoplasma GRA16, an exported dense granule protein that targets the host cell nucleus and alters gene expression. Cell Host Microbe 13:489-500. http:// dx.doi.org/10.1016/j.chom.2013.03.002.
33. Mathupala SP, Heese C, Pedersen PL. 1997. Glucose catabolism in cancer cells. The type II hexokinase promoter contains functionally active response elements for the tumor suppressor p53. J Biol Chem 272: 22776-22780. http://dx.doi.org/10.1074/jbc.272.36.22776.
34. Franco M, Shastri AJ, Boothroyd JC. 2014. Infection by Toxoplasma gondii specifically induces host c-Myc and the genes this pivotal transcription factor regulates. Eukaryot Cell 13:483-493. http://dx.doi.org/ 10.1128/EC.00316-13.
35. Kim JW, Gao P, Liu YC, Semenza GL, Dang CV. 2007. Hypoxiainducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1. Mol Cell Biol 27:7381-7393. http:// dx.doi.org/10.1128/MCB.00440-07.
36. Gottlob K, Majewski N, Kennedy S, Kandel E, Robey RB, Hay N. 2001. Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase. Genes Dev 15:1406-1418. http://dx.doi.org/10.1101/gad.889901.
37. Kim L, Denkers EY. 2006. Toxoplasma gondii triggers Gi-dependent PI 3-kinase signaling required for inhibition of host cell apoptosis. J Cell Sci 119:2119-2126. http://dx.doi.org/10.1242/jcs.02934.
38. Pastorino JG, Hoek JB, Shulga N. 2005. Activation of glycogen synthase kinase 3beta disrupts the binding of hexokinase II to mitochondria by phosphorylating voltage-dependent anion channel and potentiates chemotherapy-induced cytotoxicity. Cancer Res 65:10545-10554. http:// dx.doi.org/10.1158/0008-5472.CAN-05-1925.
39. Baggetto LG, Clottes E, Vial C. 1992. Low mitochondrial proton leak due to high membrane cholesterol content and cytosolic creatine kinase as two features of the deviant bioenergetics of Ehrlich and AS30-D tumor cells. Cancer Res 52:4935-4941.
40. Pastorino JG, Shulga N, Hoek JB. 2002. Mitochondrial binding of hexokinase II inhibits Bax-induced cytochrome c release and apoptosis. J Biol Chem 277:7610-7618. http://dx.doi.org/10.1074/jbc.M109950200.
41. Cesar Mde C, Wilson JE. 1998. Further studies on the coupling of mitochondrially bound hexokinase to intramitochondrially compartmented ATP, generated by oxidative phosphorylation. Arch Biochem Biophys 350:109-117. http://dx.doi.org/10.1006/abbi.1997.0497.
42. Ramasamy R, Vannucci SJ, Yan SS, Herold K, Yan SF, Schmidt AM. 2005. Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation. Glycobiology 15: 16R-28R. http://dx.doi.org/10.1093/glycob/cwi053.
43. Blume M, Rodriguez-Contreras D, Landfear S, Fleige T, Soldati-Favre D, Lucius R, Gupta N. 2009. Host-derived glucose and its transporter in the obligate intracellular pathogen Toxoplasma gondii are dispensable by glutaminolysis. Proc Natl Acad Sci U S A 106:12998-13003. http:// dx.doi.org/10.1073/pnas.0903831106.
44. Metheni M, Echebli N, Chaussepied M, Ransy C, Chéreau C, Jensen K, Glass E, Batteux F, Bouillaud F, Langsley G. 2014. The level of H(2)O(2) type oxidative stress regulates virulence of Theileria-transformed leukocytes. Cell Microbiol 16:269-279. http://dx.doi.org/10.1111/cmi.12218.
45. da-Silva WS, Gómez-Puyou A, de Gómez-Puyou MT, Moreno-Sanchez R, De Felice FG, de Meis L, Oliveira MF, Galina A. 2004. Mitochondrial bound hexokinase activity as a preventive antioxidant defense: steadystate ADP formation as a regulatory mechanism of membrane potential and reactive oxygen species generation in mitochondria. J Biol Chem 279: 39846-39855. http://dx.doi.org/10.1074/jbc.M403835200.
46. Varum S, Rodrigues AS, Moura MB, Momcilovic O, Easley C, Varum S, Rodrigues AS, Moura MB, Momcilovic O, Easley CA, Ramalho-Santos J, Van Houten B, Schatten G. 2011. Energy metabolism in human pluripotent stem cells and their differentiated counterparts. PLoS One 6:e20914. http://dx.doi.org/10.1371/journal.pone.0020914.
47. Palsson-McDermott EM, Curtis AM, Goel G, Lauterbach MA, Sheedy FJ, Gleeson LE, van den Bosch MW, Quinn SR, Domingo-Fernandez R, Johnston DG, Jiang JK, Israelsen WJ, Keane J, Thomas C, Clish C, Vanden Heiden M, Xavier RJ, O'Neill LA. 2015. Pyruvate kinase M2 regulates HIF-1alpha activity and IL-1beta induction and is a critical determinant of the Warburg effect in LPS-Activated macrophages. Cell Metab 21:65-80. http://dx.doi.org/10.1016/j.cmet.2014.12.005.
48. Chang CH, Curtis JD, Maggi LB, Jr., Faubert B, Villarino AV, O'Sullivan D, Huang SC, van der Windt GJ, Blagih J, Qiu J, Weber JD, Pearce EJ, Jones RG, Pearce EL. 2013. Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell 153:1239-1251. http:// dx.doi.org/10.1016/j.cell.2013.05.016.
49. Jensen KD, Wang Y, Wojno ED, Shastri AJ, Hu K, Cornel L, Boedec E, Ong YC, Chien YH, Hunter CA, Boothroyd JC, Saeij JP. 2011. Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation. Cell Host Microbe 9:472-483. http://dx.doi.org/ 10.1016/j.chom.2011.04.015.
50. Butcher BA, Fox BA, Rommereim LM, Kim SG, Maurer KJ, Yarovinsky F, Herbert DR, Bzik DJ, Denkers EY. 2011. Toxoplasma gondii rhoptry kinase ROP16 Activates STAT3 and STAT6 resulting in cytokine inhibition and arginase-1-dependent growth control. PLoS Pathog 7:e1002236. http://dx.doi.org/10.1371/journal.ppat.1002236.
51. Patil V, Zhao Y, Shah S, Fox BA, Rommereim LM, Bzik DJ, Yap GS. 2014. Co-existence of classical and alternative activation programs in macrophages responding to Toxoplasma gondii. Int J Parasitol 44: 161-164. http://dx.doi.org/10.1016/j.ijpara.2013.08.003.
52. Eustice DC, Feldman PA, Colberg-Poley AM, Buckery RM, Neubauer RH. 1991. A sensitive method for the detection of beta-galactosidase in transfected mammalian cells. Biotechniques 11:739-740, 742.
53. Phelps ED, Sweeney KR, Blader IJ. 2008. Toxoplasma gondii rhoptry discharge correlates with activation of the EGR2 host cell transcription factor. Infect Immun 76:4703-4712. http://dx.doi.org/10.1128/IAI.01447-07.
54. Charles E, Joshi S, Ash JD, Fox BA, Farris AD, Bzik DJ, Lang ML, Blader IJ. 2010. CD4 T-cell suppression by cells from Toxoplasma gondiiinfected retinas is mediated by surface protein PD-L1. Infect Immun 78: 3484-3492. http://dx.doi.org/10.1128/IAI.00117-10.