Malate dehydrogenase-2 inhibitor LW6 promotes metabolic adaptations and reduces proliferation and apoptosis in activated human T-cells

Experimental and Therapeutic Medicine

Volumn 10, Issue 5, 2015, Pages 1959-1966

  Eleftheriadis, Theodoros ^a   Pissas, Georgios ^a   Antoniadi, Georgia ^a   Liakopoulos, Vassilios ^a   Stefanidis, Ioannis ^a  

^a UNIVERSITY OF THESSALY   (Greece)

Author keywords

Apoptosis; Glucose metabolism; Glutaminolysis; Malate dehydrogenase; Proliferation; T cell

Indexed keywords

CASPASE 3; ENZYME INHIBITOR; GLUCOSE TRANSPORTER 1; HEXOKINASE; HYPOXIA INDUCIBLE FACTOR 1ALPHA; LACTATE DEHYDROGENASE; MALATE DEHYDROGENASE 2 INHIBITOR; MYC PROTEIN; POLYVINYLIDENE FLUORIDE; PROTEIN P53; PYRUVATE DEHYDROGENASE; UNCLASSIFIED DRUG;

ADULT; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CELL SURVIVAL; CITRIC ACID CYCLE; CLINICAL ARTICLE; CONTROLLED STUDY; CYTOTOXICITY; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; GLUCOSE METABOLISM; GLUTAMINOLYSIS; GLYCOLYSIS; HUMAN; HUMAN CELL; IMMUNOSTIMULATION; LYMPHOCYTE PROLIFERATION; MALE; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; T LYMPHOCYTE; WESTERN BLOTTING; XTT ASSAY;

EID: 84942253389     PISSN: 17920981     EISSN: 17921015     Source Type: Journal    
DOI: 10.3892/etm.2015.2763     Document Type: Article

References (39)

1. Wang R, Dillon CP, Shi LZ, Milasta S, Carter R, Finkelstein D, McCormick LL, Fitzgerald P, Chi H, Munger J and Green DR: The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation. Immunity 35: 871-882, 2011.
2. Wang R and Green DR: Metabolic reprogramming and metabolic dependency in T cells. Immunol Rev 249: 14-26, 2012.
3. Ostroukhova M, Goplen N, Karim MZ, Michalec L, Guo L, Liang Q and Alam R: The role of low-level lactate production in airway inflammation in asthma. Am J Physiol Lung Cell Mol Physiol 302: L300-L307, 2012.
4. Shi LZ, Wang R, Huang G, Vogel P, Neale G, Green DR and Chi H: HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med 208: 1367-1376, 2011.
5. Eleftheriadis T, Pissas G, Karioti A, Antoniadi G, Antoniadis N, Liakopoulos V and Stefanidis I: Dichloroacetate at therapeutic concentration alters glucose metabolism and induces regulatory T-cell differentiation in alloreactive human lymphocytes. J Basic Clin Physiol Pharmacol 24: 271-276, 2013.
6. Eleftheriadis T, Pissas G, Karioti A, Antoniadi G, Liakopoulos V, Dafopoulou K, Pournaras S, Koukoulis G and Stefanidis I: The indoleamine 2, 3-dioxygenase inhibitor 1-methyl-tryptophan suppresses mitochondrial function, induces aerobic glycolysis and decreases interleukin-10 production in human lymphocytes. Immunol Invest 41: 507-520, 2012.
7. Eleftheriadis T, Pissas G, Yiannaki E, Markala D, Arampatzis S, Antoniadi G, Liakopoulos V and Stefanidis I: Inhibition of indoleamine 2, 3-dioxygenase in mixed lymphocyte reaction affects glucose influx and enzymes involved in aerobic glycolysis and glutaminolysis in alloreactive T-cells. Hum Immunol 74: 1501-1509, 2013.
8. Eleftheriadis T, Pissas G, Antoniadi G, Spanoulis A, Liakopoulos V and Stefanidis I: Indoleamine 2, 3-dioxygenase increases p53 levels in alloreactive human T cells and both indoleamine 2, 3-dioxygenase and p53 suppress glucose uptake, glycolysis and proliferation. Int Immunol 26: 673-684, 2014.
9. Lee K, Kang JE, Park SK, Jin Y, Chung KS, Kim HM, Lee K, Kang MR, Lee MK, Song KB, et al: LW6, a novel HIF-1 inhibitor, promotes proteasomal degradation of HIF-1alpha via upregulation of VHL in a colon cancer cell line. Biochem Pharmacol 80: 982-989, 2010.
10. Lee K, Ban HS, Naik R, Hong YS, Son S, Kim BK, Xia Y, Song KB, Lee HS and Won M: Identification of malate dehydrogenase 2 as a target protein of the HIF-1 inhibitor LW6 using chemical probes. Angew Chem Int Ed Engl 52: 10286-10289, 2013.
11. Friedman B, Goodman EH Jr, Saunders HL, Kostos V and Weinhouse S: Estimation of pyruvate recycling during gluconeogenesis in perfused rat liver. Metabolism 20: 2-12, 1971.
12. Berridge MV, Herst PM and Tan AS: Tetrazolium dyes as tools in cell biology: New insights into their cellular reduction. Biotechnol Annu Rev 11: 127-152, 2005.
13. Dang EV, Barbi J, Yang HY, Jinasena D, Yu H, Zheng Y, Bordman Z, Fu J, Kim Y and Yen HR: Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell 146: 772-784, 2011.
14. Guy CS, Vignali KM, Temirov J, Bettini ML, Overacre AE, Smeltzer M, Zhang H, Huppa JB, Tsai YH, Lobry C, et al: Distinct TCR signaling pathways drive proliferation and cytokine production in T cells. Nat Immunol 14: 262-270, 2013.
15. Doe MR, Ascano JM, Kaur M and Cole MD: Myc posttranscriptionally induces HIF1 protein and target gene expression in normal and cancer cells. Cancer Res 72: 949-957, 2012.
16. Chen C, Cai S, Wang G, Cao X, Yang X, Luo X, Feng Y and Hu J: c-Myc enhances colon cancer cell-mediated angiogenesis through the regulation of HIF-1α. Biochem Biophys Res Commun 430: 505-511, 2013.
17. Podar K and Anderson KC: A therapeutic role for targeting c-Myc/Hif-1-dependent signaling pathways. Cell Cycle 9: 1722-1728, 2010.
18. Hong KS, Park JI, Kim MJ, Kim HB, Lee JW, Dao TT, Oh WK, Kang CD and Kim SH: Involvement of SIRT1 in hypoxic down-regulation of c-Myc and β-catenin and hypoxic preconditioning effect of polyphenols. Toxicol Appl Pharmacol 259: 210-218, 2012.
19. Huang LE: Carrot and stick: HIF-alpha engages c-Myc in hypoxic adaptation. Cell Death Differ 15: 672-677, 2008.
20. Li Q, Kluz T, Sun H and Costa M: Mechanisms of c-myc degradation by nickel compounds and hypoxia. PloS One 4: e8531, 2009.
21. Sermeus A and Michiels C: Reciprocal influence of the p53 and the hypoxic pathways. Cell Death Dis 2: e164, 2011.
22. Eischen CM, Weber JD, Roussel MF, Sherr CJ and Cleveland JL: Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis. Genes Dev 13: 2658-2669, 1999.
23. Brady CA and Attardi LD: p53 at a glance. J Cell Sci 123: 2527-2532, 2010.
24. Green DR and Kroemer G: Cytoplasmic functions of the tumour suppressor p53. Nature 458: 1127-1130, 2009.
25. Iyer NV, Kotch LE, Agani F, Leung SW, Laughner E, Wenger RH, Gassmann M, Gearhart JD, Lawler AM, Yu AY and Semenza GL: Cellular and developmental control of O2homeostasis by hypoxia-inducible factor 1 alpha. Genes Dev 12: 149-162, 1998.
26. Osthus RC, Shim H, Kim S, Li Q, Reddy R, Mukherjee M, Xu Y, Wonsey D, Lee LA and Dang CV: Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc. J Biol Chem 275: 21797-21800, 2000.
27. Gordan JD, Thompson CB and Simon MC: HIF and c-Myc: Sibling rivals for control of cancer cell metabolism and proliferation. Cancer Cell 12: 108-113, 2007.
28. Valera A, Pujol A, Gregori X, Riu E, Visa J and Bosch F: Evidence from transgenic mice that myc regulates hepatic glycolysis. FASEB J 9: 1067-1078, 1995.
29. Shim H, Dolde C, Lewis BC, Wu CS, Dang G, Jungmann RA, Dalla-Favera R and Dang CV: c-Myc transactivation of LDH-A: Implications for tumor metabolism and growth. Proc Natl Acad Sci USA 94: 6658-6663, 1997.
30. Korotchkina LG and Patel MS: Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward the three phosphorylation sites of human pyruvate dehydrogenase. J Biol Chem 276: 37223-37229, 2001.
31. Kim JW, Tchernyshyov I, Semenza GL and Dang CV: HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia. Cell Metab 3: 177-185, 2006.
32. Munger J, Bajad SU, Coller HA, Shenk T and Rabinowitz JD: Dynamics of the cellular metabolome during human cytomegalovirus infection. PLoS Pathog 2: e132, 2006.
33. Le A, Lane AN, Hamaker M, Bose S, Gouw A, Barbi J, Tsukamoto T, Rojas CJ, Slusher BS, Zhang H, et al: Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells. Cell Metab 15: 110-121, 2012.
34. Yang C, Ko B, Hensley CT, Jiang L, Wasti AT, Kim J, Sudderth J, Calvaruso MA, Lumata L, Mitsche M, et al: Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport. Mol Cell 56: 414-424, 2014.
35. Mates JM, Segura JA, Martin-Rufián M, Campos-Sandoval JA, Alonso FJ and Marquez J: Glutaminase isoenzymes as key regulators in metabolic and oxidative stress against cancer. Curr Mol Med 13: 514-534, 2013.
36. Colombo SL, Palacios-Callender M, Frakich N, De Leon J, Schmitt CA, Boorn L, Davis N and Moncada S: Anaphase-promoting complex/cyclosome-Cdh1 coordinates glycolysis and glutaminolysis with transition to S phase in human T lymphocytes. Proc Natl Acad Sci USA 107: 18868-18873, 2010.
37. Gao P, Tchernyshyov I, Chang TC, Lee YS, Kita K, Ochi T, Zeller KI, De Marzo AM, Van Eyk JE, Mendell JT and Dang CV: c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 458: 762-765, 2009.
38. Suzuki S, Tanaka T, Poyurovsky MV, Nagano H, Mayama T, Ohkubo S, Lokshin M, Hosokawa H, Nakayama T, Suzuki Y, et al: Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species. Proc Natl Acad Sci USA 107: 7461-7466, 2010.
39. Hu W, Zhang C, Wu R, Sun Y, Levine A and Feng Z: Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. Proc Natl Acad Sci USA 107: 7455-7460, 2010.