Cardiovascular Drugs and Therapy

, Volume 28, Issue 4, pp 347–360

Thioredoxin-Interacting Protein: Pathophysiology and Emerging Pharmacotherapeutics in Cardiovascular Disease and Diabetes

  • Cher-Rin Chong
  • Wai Ping A. Chan
  • Thanh H. Nguyen
  • Saifei Liu
  • Nathan E. K. Procter
  • Doan T. Ngo
  • Aaron L. Sverdlov
  • Yuliy Y. Chirkov
  • John D. Horowitz
REVIEW ARTICLE

Abstract

The thioredoxin system, which consists of thioredoxin (Trx), nicotinamide adenine dinucleotide phosphate (NADPH) and thioredoxin reductase (TrxR), has emerged as a major anti-oxidant involved in the maintenance of cellular physiology and survival. Dysregulation in this system has been associated with metabolic, cardiovascular, and malignant disorders. Thioredoxin-interacting protein (TXNIP), also known as vitamin D-upregulated protein or thioredoxin-binding-protein-2, functions as a physiological inhibitor of Trx, and pathological suppression of Trx by TXNIP has been demonstrated in diabetes and cardiovascular diseases. Furthermore, TXNIP effects are partially Trx-independent; these include direct activation of inflammation and inhibition of glucose uptake. Many of the effects of TXNIP are initiated by its dissociation from intra-nuclear binding with Trx or other SH-containing proteins: these effects include its migration to cytoplasm, modulating stress responses in mitochondria and endoplasmic reticulum, and also potentially activating apoptotic pathways. TXNIP also interacts with the nitric oxide (NO) signaling system, with apparent suppression of NO effect. TXNIP production is modulated by redox stress, glucose levels, hypoxia and several inflammatory activators. In recent studies, it has been shown that therapeutic agents including insulin, metformin, angiotensin converting enzyme inhibitors and calcium channel blockers reduce TXNIP expression, although it is uncertain to what extent TXNIP suppression contributes to their clinical efficacy. This review addresses the role of TXNIP in health and in cardiovascular and metabolic disorders. Finally, the potential advantages (and disadvantages) of pharmacological suppression of TXNIP in cardiovascular disease and diabetes are summarized

Keywords

Thioredoxin-interacting protein Thioredoxin Diabetes Cardiovascular diseases Oxidative stress Inflammation Nitric oxide Therapeutics 

References

  1. 1.
    Lee S, Kim SM, Lee RT. Thioredoxin and thioredoxin target proteins: from molecular mechanisms to functional significance. Antioxid Redox Signal. 2013;18:1165–207.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Nishiyama A, Matsui M, Iwata S, et al. Identification of thioredoxin-binding protein-2/vitamin D (3) up-regulated protein 1 as a negative regulator of thioredoxin function and expression. J Biol Chem. 1999;274:21645–50.PubMedCrossRefGoogle Scholar
  3. 3.
    Patwari P, Higgins LJ, Chutkow WA, Yoshioka J, Lee RT. The interaction of thioredoxin with Txnip evidence for formation of a mixed disulfide by disulfide exchange. J Biol Chem. 2006;281:21884–91.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Patwari P, Chutkow WA, Cummings K, et al. Thioredoxin-independent regulation of metabolism by the alpha-arrestin proteins. J Biol Chem. 2009;284:24996–5003.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Laporte SA, Oakley RH, Holt JA, Barak LS, Caron MG. The interaction of beta-arrestin with the AP-2 adaptor is required for the clustering of beta 2-adrenergic receptor into clathrin-coated pits. J Biol Chem. 2000;275:23120–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Luttrell LM, Ferguson SS, Daaka Y, et al. Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes. Science (New York, NY) 1999;283:655–61.Google Scholar
  7. 7.
    Patwari P, Lee RT. An expanded family of arrestins regulate metabolism. Trends Endocrinol Metab TEM. 2012;23:216–22.CrossRefGoogle Scholar
  8. 8.
    Junn E, Han SH, Im JY, et al. Vitamin D3 up-regulated protein 1 mediates oxidative stress via suppressing the thioredoxin function. Journal of immunology (Baltimore, Md : 1950) 2000;164:6287–95.Google Scholar
  9. 9.
    Schulze PC, Yoshioka J, Takahashi T, He Z, King GL, Lee RT. Hyperglycemia promotes oxidative stress through inhibition of thioredoxin function by thioredoxin-interacting protein. J Biol Chem. 2004;279:30369–74.PubMedCrossRefGoogle Scholar
  10. 10.
    Saxena G, Chen J, Shalev A. Intracellular shuttling and mitochondrial function of thioredoxin-interacting protein. J Biol Chem. 2010;285:3997–4005.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    World C, Spindel ON, Berk BC. Thioredoxin-interacting protein mediates TRX1 translocation to the plasma membrane in response to tumor necrosis factor-alpha: a key mechanism for vascular endothelial growth factor receptor-2 transactivation by reactive oxygen species. Arterioscler Thromb Vasc Biol. 2011;31:1890–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Spindel ON, Yan C, Berk BC. Thioredoxin-interacting protein mediates nuclear-to-plasma membrane communication: role in vascular endothelial growth factor 2 signaling. Arterioscler Thromb Vasc Biol. 2012;32:1264–70.PubMedCrossRefGoogle Scholar
  13. 13.
    Lane T, Flam B, Lockey R, Kolliputi N. TXNIP shuttling: missing link between oxidative stress and inflammasome activation. Front Physiol. 2013;4:50.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Lee S, Min Kim S, Dotimas J, et al. Thioredoxin-interacting protein regulates protein disulfide isomerases and endoplasmic reticulum stress. EMBO molecular medicine 2014.Google Scholar
  15. 15.
    Oslowski CM, Hara T, O’Sullivan-Murphy B, et al. Thioredoxin-interacting protein mediates ER stress-induced beta cell death through initiation of the inflammasome. Cell Metab. 2012;16:265–73.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Lerner AG, Upton JP, Praveen PV, et al. IRE1alpha induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress. Cell Metab. 2012;16:250–64.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Park SY, Shi X, Pang J, Yan C, Berk BC. Thioredoxin-interacting protein mediates sustained VEGFR2 signaling in endothelial cells required for angiogenesis. Arterioscler Thromb Vasc Biol. 2013;33:737–43.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Forrester MT, Seth D, Hausladen A, et al. Thioredoxin-interacting protein (Txnip) is a feedback regulator of S-nitrosylation. J Biol Chem. 2009;284:36160–6.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Nadeau PJ, Charette SJ, Toledano MB, Landry J. Disulfide bond-mediated multimerization of Ask1 and its reduction by thioredoxin-1 regulate H (2) O (2)-induced c-Jun NH (2)-terminal kinase activation and apoptosis. Mol Biol Cell. 2007;18:3903–13.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Xiang G, Seki T, Schuster MD, et al. Catalytic degradation of vitamin D up-regulated protein 1 mRNA enhances cardiomyocyte survival and prevents left ventricular remodeling after myocardial ischemia. J Biol Chem. 2005;280:39394–402.PubMedCrossRefGoogle Scholar
  21. 21.
    Zhang P, Wang C, Gao K, et al. The ubiquitin ligase itch regulates apoptosis by targeting thioredoxin-interacting protein for ubiquitin-dependent degradation. J Biol Chem. 2010;285:8869–79.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Ago T, Liu T, Zhai P, et al. A redox-dependent pathway for regulating class II HDACs and cardiac hypertrophy. Cell. 2008;133:978–93.PubMedCrossRefGoogle Scholar
  23. 23.
    He X, Ma Q. Redox regulation by nuclear factor erythroid 2-related factor 2: gatekeeping for the basal and diabetes-induced expression of thioredoxin-interacting protein. Mol Pharmacol. 2012;82:887–97.PubMedCrossRefGoogle Scholar
  24. 24.
    Shah A, Xia L, Goldberg H, Lee KW, Quaggin SE, Fantus IG. Thioredoxin-interacting protein mediates high glucose-induced reactive oxygen species generation by mitochondria and the NADPH oxidase, Nox4, in mesangial cells. J Biol Chem. 2013;288:6835–48.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Mohamed IN, Hafez SS, Fairaq A, Ergul A, Imig JD, El-Remessy AB. Thioredoxin-interacting protein is required for endothelial NLRP3 inflammasome activation and cell death in a rat model of high-fat diet. Diabetologia. 2014;57:413–23.PubMedCrossRefGoogle Scholar
  26. 26.
    Wang XQ, Nigro P, World C, Fujiwara K, Yan C, Berk BC. Thioredoxin interacting protein promotes endothelial cell inflammation in response to disturbed flow by increasing leukocyte adhesion and repressing Kruppel-like factor 2. Circ Res. 2012;110:560–8.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Yamawaki H, Pan S, Lee RT, Berk BC. Fluid shear stress inhibits vascular inflammation by decreasing thioredoxin-interacting protein in endothelial cells. J Clin Invest. 2005;115:733–8.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Spindel ON, Burke RM, Yan C, Berk BC. Thioredoxin-interacting protein is a biomechanical regulator of Src activity: key role in endothelial cell stress fiber formation. Circ Res. 2014;114:1125–32.PubMedCrossRefGoogle Scholar
  29. 29.
    Wang Y, De Keulenaer GW, Lee RT. Vitamin D (3)-up-regulated protein-1 is a stress-responsive gene that regulates cardiomyocyte viability through interaction with thioredoxin. J Biol Chem. 2002;277:26496–500.PubMedCrossRefGoogle Scholar
  30. 30.
    Yoshioka J, Imahashi K, Gabel SA, et al. Targeted deletion of thioredoxin-interacting protein regulates cardiac dysfunction in response to pressure overload. Circ Res. 2007;101:1328–38.PubMedCrossRefGoogle Scholar
  31. 31.
    Yu Y, Xing K, Badamas R, Kuszynski CA, Wu H, Lou MF. Overexpression of thioredoxin-binding protein 2 increases oxidation sensitivity and apoptosis in human lens epithelial cells. Free Radic Biol Med. 2013;57:92–104.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Wong RW, Hagen T. Mechanistic target of rapamycin (mTOR) dependent regulation of thioredoxin interacting protein (TXNIP) transcription in hypoxia. Biochem Biophys Res Commun. 2013;433:40–6.PubMedCrossRefGoogle Scholar
  33. 33.
    Farrell MR, Rogers LK, Liu Y, Welty SE, Tipple TE. Thioredoxin-interacting protein inhibits hypoxia-inducible factor transcriptional activity. Free Radic Biol Med. 2010;49:1361–7.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Park YJ, Yoon SJ, Suh HW, et al. TXNIP deficiency exacerbates endotoxic shock via the induction of excessive nitric oxide synthesis. PLoS Pathog. 2013;9:e1003646.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Zhang H, Luo Y, Zhang W, et al. Endothelial-specific expression of mitochondrial thioredoxin improves endothelial cell function and reduces atherosclerotic lesions. Am J Pathol. 2007;170:1108–20.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Schulze PC, Liu H, Choe E, et al. Nitric oxide-dependent suppression of thioredoxin-interacting protein expression enhances thioredoxin activity. Arterioscler Thromb Vasc Biol. 2006;26:2666–72.PubMedCrossRefGoogle Scholar
  37. 37.
    Shaked M, Ketzinel-Gilad M, Ariav Y, Cerasi E, Kaiser N, Leibowitz G. Insulin counteracts glucotoxic effects by suppressing thioredoxin-interacting protein production in INS-1E beta cells and in Psammomys obesus pancreatic islets. Diabetologia. 2009;52:636–44.PubMedCrossRefGoogle Scholar
  38. 38.
    Sverdlov AL, Chan WP, Procter NE, Chirkov YY, Ngo DT, Horowitz JD. Reciprocal regulation of NO signaling and TXNIP expression in humans: Impact of aging and ramipril therapy. Int J Cardiol. 2013;168:4624–30.PubMedCrossRefGoogle Scholar
  39. 39.
    Spindel ON, World C, Berk BC. Thioredoxin interacting protein: redox dependent and independent regulatory mechanisms. Antioxid Redox Signal. 2012;16:587–96.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Yoshioka J, Chutkow WA, Lee S, et al. Deletion of thioredoxin-interacting protein in mice impairs mitochondrial function but protects the myocardium from ischemia-reperfusion injury. J Clin Invest. 2012;122:267–79.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Yoshioka J, Lee RT. Thioredoxin-interacting protein and myocardial mitochondrial function in ischemia-reperfusion injury. Trends Cardiovasc Med. 2014;24:75–80.PubMedCrossRefGoogle Scholar
  42. 42.
    Shalev A, Pise-Masison CA, Radonovich M, et al. Oligonucleotide microarray analysis of intact human pancreatic islets: identification of glucose-responsive genes and a highly regulated TGFbeta signaling pathway. Endocrinology. 2002;143:3695–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat Immunol. 2010;11:136–40.PubMedCrossRefGoogle Scholar
  44. 44.
    Luo B, Li B, Wang W, et al. Rosuvastatin alleviates diabetic cardiomyopathy by inhibiting NLRP3 inflammasome and MAPK pathways in a type 2 diabetes rat model. Cardiovasc Drugs Ther. 2014;28:33–43.PubMedCrossRefGoogle Scholar
  45. 45.
    Singh LP. The NLRP3 inflammasome and diabetic cardiomyopathy : editorial to: “Rosuvastatin alleviates diabetic cardiomyopathy by inhibiting NLRP3 inflammasome and MAPK pathways in a type 2 diabetes rat model” by Beibei Luo et al. Cardiovasc Drugs Ther. 2014;28:5–6.PubMedCrossRefGoogle Scholar
  46. 46.
    Schroder K, Zhou R, Tschopp J. The NLRP3 inflammasome: a sensor for metabolic danger? Science (New York, NY) 2010;327:296–300.Google Scholar
  47. 47.
    Davis BK, Ting JP. NLRP3 has a sweet tooth. Nat Immunol. 2010;11:105–6.PubMedCrossRefGoogle Scholar
  48. 48.
    Perrone L, Devi TS, Hosoya KI, Terasaki T, Singh LP. Inhibition of TXNIP expression in vivo blocks early pathologies of diabetic retinopathy. Cell death Dis. 2010;1:e65.PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Chen J, Cha-Molstad H, Szabo A, Shalev A. Diabetes induces and calcium channel blockers prevent cardiac expression of proapoptotic thioredoxin-interacting protein. Am J Physiol Endocrinol Metab. 2009;296:E1133–9.PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Tan SM, Zhang Y, Cox AJ, Kelly DJ, Qi W. Tranilast attenuates the up-regulation of thioredoxin-interacting protein and oxidative stress in an experimental model of diabetic nephropathy nephrology, dialysis, transplantation official publication of the European dialysis and transplant association. Eur Ren Assoc. 2011;26:100–10.Google Scholar
  51. 51.
    Malmberg K, Ryden L, Hamsten A, Herlitz J, Waldenstrom A, Wedel H. Effects of insulin treatment on cause-specific one-year mortality and morbidity in diabetic patients with acute myocardial infarction DIGAMI study group diabetes insulin-glucose in acute myocardial infarction. Eur Heart J. 1996;17:1337–44.PubMedCrossRefGoogle Scholar
  52. 52.
    Worthley MI, Holmes AS, Willoughby SR, et al. The deleterious effects of hyperglycemia on platelet function in diabetic patients with acute coronary syndromes mediation by superoxide production, resolution with intensive insulin administration. J Am Coll Cardiol. 2007;49:304–10.PubMedCrossRefGoogle Scholar
  53. 53.
    Piwkowska A, Rogacka D, Audzeyenka I, Angielski S, Jankowski M. High glucose increases glomerular filtration barrier permeability by activating protein kinase G type Ialpha subunits in a Nox4-dependent manner. Exp Cell Res. 2014;320:144–52.PubMedCrossRefGoogle Scholar
  54. 54.
    Ludwig DL, Kotanides H, Le T, Chavkin D, Bohlen P, Witte L. Cloning, genetic characterization, and chromosomal mapping of the mouse VDUP1 gene. Gene. 2001;269:103–12.PubMedCrossRefGoogle Scholar
  55. 55.
    Oka S, Masutani H, Liu W, et al. Thioredoxin-binding protein-2-like inducible membrane protein is a novel vitamin D3 and peroxisome proliferator-activated receptor (PPAR) gamma ligand target protein that regulates PPARgamma signaling. Endocrinology. 2006;147:733–43.PubMedCrossRefGoogle Scholar
  56. 56.
    Oka S, Yoshihara E, Bizen-Abe A, et al. Thioredoxin binding protein-2/thioredoxin-interacting protein is a critical regulator of insulin secretion and peroxisome proliferator-activated receptor function. Endocrinology. 2009;150:1225–34.PubMedCrossRefGoogle Scholar
  57. 57.
    Minn AH, Hafele C, Shalev A. Thioredoxin-interacting protein is stimulated by glucose through a carbohydrate response element and induces beta-cell apoptosis. Endocrinology. 2005;146:2397–405.PubMedCrossRefGoogle Scholar
  58. 58.
    Masutani H, Yoshihara E, Masaki S, Chen Z, Yodoi J. Thioredoxin binding protein (TBP)-2/Txnip and alpha-arrestin proteins in cancer and diabetes mellitus. J Clin Biochem Nutr. 2012;50:23–34.PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Han SH, Jeon JH, Ju HR, et al. VDUP1 upregulated by TGF-beta1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression. Oncogene. 2003;22:4035–46.PubMedCrossRefGoogle Scholar
  60. 60.
    Masaki S, Masutani H, Yoshihara E, Yodoi J. Deficiency of thioredoxin binding protein-2 (TBP-2) enhances TGF-beta signaling and promotes epithelial to mesenchymal transition. PLoS One. 2012;7:e39900.PubMedCentralPubMedCrossRefGoogle Scholar
  61. 61.
    Robinson KA, Brock JW, Buse MG. Posttranslational regulation of thioredoxin-interacting protein. J Mol Endocrinol. 2013;50:59–71.PubMedCrossRefGoogle Scholar
  62. 62.
    Wu N, Zheng B, Shaywitz A, et al. AMPK-dependent degradation of TXNIP upon energy stress leads to enhanced glucose uptake via GLUT1. Mol Cell. 2013;49:1167–75.PubMedCentralPubMedCrossRefGoogle Scholar
  63. 63.
    Viollet B, Guigas B, Leclerc J, et al. AMP-activated protein kinase in the regulation of hepatic energy metabolism: from physiology to therapeutic perspectives. Acta physiologica (Oxford, England) 2009;196:81–98.Google Scholar
  64. 64.
    Shaked M, Ketzinel-Gilad M, Cerasi E, Kaiser N, Leibowitz G. AMP-activated protein kinase (AMPK) mediates nutrient regulation of thioredoxin-interacting protein (TXNIP) in pancreatic beta-cells. PLoS One. 2011;6:e28804.PubMedCentralPubMedCrossRefGoogle Scholar
  65. 65.
    Nishizawa K, Nishiyama H, Matsui Y, et al. Thioredoxin-interacting protein suppresses bladder carcinogenesis. Carcinogenesis. 2011;32:1459–66.PubMedCrossRefGoogle Scholar
  66. 66.
    Kwon HJ, Won YS, Suh HW, et al. Vitamin D3 upregulated protein 1 suppresses TNF-alpha-induced NF-kappaB activation in hepatocarcinogenesis. Journal of immunology (Baltimore, Md : 1950) 2010;185:3980–9.Google Scholar
  67. 67.
    Ellis L, Hammers H, Pili R. Targeting tumor angiogenesis with histone deacetylase inhibitors. Cancer Lett. 2009;280:145–53.PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Lee JH, Jeong EG, Choi MC, et al. Inhibition of histone deacetylase 10 induces thioredoxin-interacting protein and causes accumulation of reactive oxygen species in SNU-620 human gastric cancer cells. Macromolecule Cells. 2010;30:107–12.CrossRefGoogle Scholar
  69. 69.
    Chen J, Saxena G, Mungrue IN, Lusis AJ, Shalev A. Thioredoxin-interacting protein: a critical link between glucose toxicity and beta-cell apoptosis. Diabetes. 2008;57:938–44.PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    Shao W, Yu Z, Fantus IG, Jin T. Cyclic AMP signaling stimulates proteasome degradation of thioredoxin interacting protein (TxNIP) in pancreatic beta-cells. Cell Signal. 2010;22:1240–6.PubMedCrossRefGoogle Scholar
  71. 71.
    Parikh H, Carlsson E, Chutkow WA, et al. TXNIP regulates peripheral glucose metabolism in humans. PLoS Med. 2007;4:e158.PubMedCentralPubMedCrossRefGoogle Scholar
  72. 72.
    Chen J, Couto FM, Minn AH, Shalev A. Exenatide inhibits beta-cell apoptosis by decreasing thioredoxin-interacting protein. Biochem Biophys Res Commun. 2006;346:1067–74.PubMedCrossRefGoogle Scholar
  73. 73.
    Chai TF, Hong SY, He H, et al. A potential mechanism of metformin-mediated regulation of glucose homeostasis: inhibition of thioredoxin-interacting protein (Txnip) gene expression. Cell Signal. 2012;24:1700–5.PubMedCrossRefGoogle Scholar
  74. 74.
    Chirkov YY, Horowitz JD. Impaired tissue responsiveness to organic nitrates and nitric oxide: a new therapeutic frontier? Pharmacol Ther. 2007;116:287–305.PubMedCrossRefGoogle Scholar
  75. 75.
    Ngo DT, Stafford I, Kelly DJ, et al. Vitamin D (2) supplementation induces the development of aortic stenosis in rabbits: interactions with endothelial function and thioredoxin-interacting protein. Eur J Pharmacol. 2008;590:290–6.PubMedCrossRefGoogle Scholar
  76. 76.
    Ngo DT, Stafford I, Sverdlov AL, et al. Ramipril retards development of aortic valve stenosis in a rabbit model: mechanistic considerations. Br J Pharmacol. 2011;162:722–32.PubMedCentralPubMedCrossRefGoogle Scholar
  77. 77.
    Wu J, Lin H, Liu D, et al. The protective effect of telmisartan in Type 2 diabetes rat kidneys is related to the downregulation of thioredoxin-interacting protein. J Endocrinol Investig. 2013;36:453–9.Google Scholar
  78. 78.
    Ngo DT, Drury NE, Pagano D, Frenneaux MP, Horowitz JD. How does perhexiline maleate modulate myocardial energetics and ameliorate redox stress? Circulation. 2011;12, A14461.Google Scholar
  79. 79.
    Liberts EA, Willoughby SR, Kennedy JA, Horowitz JD. Effects of perhexiline and nitroglycerin on vascular, neutrophil and platelet function in patients with stable angina pectoris. Eur J Pharmacol. 2007;560:49–55.PubMedCrossRefGoogle Scholar
  80. 80.
    Lee L, Campbell R, Scheuermann-Freestone M, et al. Metabolic modulation with perhexiline in chronic heart failure: a randomized, controlled trial of short-term use of a novel treatment. Circulation. 2005;112:3280–8.PubMedCrossRefGoogle Scholar
  81. 81.
    Balgi AD, Fonseca BD, Donohue E, et al. Screen for chemical modulators of autophagy reveals novel therapeutic inhibitors of mTORC1 signaling. PLoS One. 2009;4:e7124.PubMedCentralPubMedCrossRefGoogle Scholar
  82. 82.
    Xu G, Chen J, Jing G, Shalev A. Preventing beta-cell loss and diabetes with calcium channel blockers. Diabetes. 2012;61:848–56.PubMedCentralPubMedCrossRefGoogle Scholar
  83. 83.
    Tarif N, Bakris GL. Preservation of renal function: the spectrum of effects by calcium-channel blockers nephrology, dialysis, transplantation : official publication of the European dialysis and transplant association. Eur Ren Assoc. 1997;12:2244–50.Google Scholar
  84. 84.
    Cooper-Dehoff R, Cohen JD, Bakris GL, et al. Predictors of development of diabetes mellitus in patients with coronary artery disease taking antihypertensive medications (findings from the INternational VErapamil SR-Trandolapril STudy [INVEST]). Am J Cardiol. 2006;98:890–4.PubMedCrossRefGoogle Scholar
  85. 85.
    Burger AJ, Mannino S. 5-Fluorouracil-induced coronary vasospasm. Am Heart J. 1987;114:433–6.PubMedCrossRefGoogle Scholar
  86. 86.
    Connolly S, Scott P, Cochrane D, Harte R. A case report of 5-fluorouracil-induced coronary artery vasospasm. Ulster Med J. 2010;79:135–6.PubMedCentralPubMedGoogle Scholar
  87. 87.
    Kim SM, Kwak CH, Lee B, et al. A case of severe coronary spasm associated with 5-fluorouracil chemotherapy. Korean J Intern Med. 2012;27:342–5.PubMedCentralPubMedCrossRefGoogle Scholar
  88. 88.
    Yamaguchi F, Kamitori K, Sanada K, et al. Rare sugar D-allose enhances anti-tumor effect of 5-fluorouracil on the human hepatocellular carcinoma cell line HuH-7. J Biosci Bioeng. 2008;106:248–52.PubMedCrossRefGoogle Scholar
  89. 89.
    Sandhu SK, Yap TA, de Bono JS. The emerging role of poly (ADP-Ribose) polymerase inhibitors in cancer treatment. Curr Drug Targets. 2011;12:2034–44.PubMedCrossRefGoogle Scholar
  90. 90.
    Zhang LQ, Qi GX, Jiang DM, Tian W, Zou JL. Increased poly (ADP-ribosyl) ation in peripheral leukocytes and the reperfused myocardium tissue of rats with ischemia/reperfusion injury: prevention by 3-aminobenzamide treatment. Shock (Augusta, Ga) 2012;37:492–500.Google Scholar
  91. 91.
    Yamazaki K, Tanaka S, Sakata R, et al. Protective effect of cardioplegia with poly (ADP-ribose) polymerase-1 inhibitor against myocardial ischemia-reperfusion injury: in vitro study of isolated rat heart model. J Enzym Inhib Med chem. 2013;28:143–7.CrossRefGoogle Scholar
  92. 92.
    Tao R, Kim SH, Honbo N, Karliner JS, Alano CC. Minocycline protects cardiac myocytes against simulated ischemia-reperfusion injury by inhibiting poly (ADP-ribose) polymerase-1. J Cardiovasc Pharmacol. 2010;56:659–68.PubMedCentralPubMedCrossRefGoogle Scholar
  93. 93.
    Jung KA, Kwak MK. The Nrf2 system as a potential target for the development of indirect antioxidants. Molecules (Basel, Switzerland) 2010;15:7266–91.Google Scholar
  94. 94.
    de Zeeuw D, Akizawa T, Audhya P, et al. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. N Engl J Med. 2013;369:2492–503.PubMedCrossRefGoogle Scholar
  95. 95.
    Rogers NM, Stephenson MD, Kitching AR, Horowitz JD, Coates PT. Amelioration of renal ischaemia-reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells. Br J Pharmacol. 2012;166:194–209.PubMedCentralPubMedCrossRefGoogle Scholar
  96. 96.
    Nivet-Antoine V, Cottart CH, Lemarechal H, et al. trans-Resveratrol downregulates Txnip overexpression occurring during liver ischemia-reperfusion. Biochimie 2010;92:1766–71.Google Scholar
  97. 97.
    Mousa SA, Gallati C, Simone T, et al. Dual targeting of the antagonistic pathways mediated by Sirt1 and TXNIP as a putative approach to enhance the efficacy of anti-aging interventions. Aging. 2009;1:412–24.PubMedCentralPubMedGoogle Scholar
  98. 98.
    Butler LM, Zhou X, Xu WS, et al. The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin. Proc Natl Acad Sci U S A. 2002;99:11700–5.PubMedCentralPubMedCrossRefGoogle Scholar
  99. 99.
    Zhou J, Bi C, Cheong LL, et al. The histone methyltransferase inhibitor, DZNep, up-regulates TXNIP, increases ROS production, and targets leukemia cells in AML. Blood. 2011;118:2830–9.PubMedCrossRefGoogle Scholar
  100. 100.
    Sipahi I, Debanne SM, Rowland DY, Simon DI, Fang JC. Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. lancet Oncol. 2010;11:627–36.PubMedCentralPubMedCrossRefGoogle Scholar
  101. 101.
    Rao GA, Mann JR, Bottai M, et al. Angiotensin receptor blockers and risk of prostate cancer among United States veterans. J Clin Pharmacol. 2013;53:773–8.PubMedCentralPubMedCrossRefGoogle Scholar
  102. 102.
    Sorensen GV, Ganz PA, Cole SW, et al. Use of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and risk of breast cancer recurrence: a Danish nationwide prospective cohort study. Int J Clin Oncol : off J Clin Oncol Off J Am Soc Clin Oncol. 2013;31:2265–72.CrossRefGoogle Scholar
  103. 103.
    Bhaskaran K, Douglas I, Evans S, van Staa T, Smeeth L. Angiotensin receptor blockers and risk of cancer: cohort study among people receiving antihypertensive drugs in UK General Practice Research Database. BMJ (Clinical research ed) 2012;344:e2697.Google Scholar
  104. 104.
    Cha-Molstad H, Xu G, Chen J, et al. Calcium channel blockers act through nuclear factor Y to control transcription of key cardiac genes. Mol Pharmacol. 2012;82:541–9.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Cher-Rin Chong
    • 1
  • Wai Ping A. Chan
    • 1
  • Thanh H. Nguyen
    • 1
  • Saifei Liu
    • 1
  • Nathan E. K. Procter
    • 1
  • Doan T. Ngo
    • 1
  • Aaron L. Sverdlov
    • 1
  • Yuliy Y. Chirkov
    • 1
  • John D. Horowitz
    • 1
    • 2
  1. 1.Cardiology and Clinical Pharmacology Department, Basil Hetzel InstituteQueen Elizabeth Hospital, University of AdelaideAdelaideAustralia
  2. 2.Cardiology DepartmentQueen Elizabeth HospitalWoodvilleSouth Australia

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