|Year : 2015 | Volume
| Issue : 1 | Page : 26-30
Thioredoxin-interacting Protein as a Common Regulation Target for Multiple Drugs in Clinical Therapy/Application
Pengxing Zhang1, Xiaoling Pang2, Yanyang Tu3
1 Department of Experimental Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China
2 Department of Emergency, The Fourth Affiliated Hospital, China Medical University, Shenyang, Liaoning, China; Department of Biochemistry and Molecular Biology, Division of Molecular Medical Biochemistry, Shiga University of Medical Sciences, Shiga, Japan
3 Department of Experimental Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China; Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
|Date of Submission||12-Jan-2015|
|Date of Acceptance||05-Feb-2015|
|Date of Web Publication||16-Feb-2015|
Prof. Yanyang Tu
Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
Source of Support: None, Conflict of Interest: None
Initially identified in HL60 cells treated with Vitamin D3, thioredoxin-interacting protein (TXNIP) is considered as a major redox regulator and a potential connector between cellular redox state and metabolism. TXNIP plays an important role in the control of glucose and lipid metabolism, and it has been defined as a tumor suppressor gene in various solid tumors and hematological malignancies. This review gives an overview of the mechanism of various medicines including Lycium barbarum polysaccharide, Quercetin, trans-resveratrol, metformin, purple sweet potato color, nobiletin, taurine, suberoylanilide hydroxamic acid, and Theophylline, and their potential applications in the clinical treatment of many diseases.
Keywords: Clinical treatment, medicines, NLRP3 inﬂammasome, redox regulation, thioredoxin-interacting protein
|How to cite this article:|
Zhang P, Pang X, Tu Y. Thioredoxin-interacting Protein as a Common Regulation Target for Multiple Drugs in Clinical Therapy/Application. Cancer Transl Med 2015;1:26-30
|How to cite this URL:|
Zhang P, Pang X, Tu Y. Thioredoxin-interacting Protein as a Common Regulation Target for Multiple Drugs in Clinical Therapy/Application. Cancer Transl Med [serial online] 2015 [cited 2019 Jan 17];1:26-30. Available from: http://www.cancertm.com/text.asp?2015/1/1/26/151488
| Introduction|| |
Mostly malignant tumor represents a form of incurable medical disorder with poor prognosis. It compromises the life quality of the patients worldwide. Along with the development of clinical medicine, the regulatory mechanisms of tumor formation process and the pathogenesis of various solid tumors or hematologic malignancies have been most heavily studied.  Therefore, researchers are clearly aware that tumor metabolic pathways are becoming important molecular targets for cancer therapy. The molecular mechanisms of many traditional drug treatments were found to participate in different metabolic pathways. Thioredoxin-interacting protein (TXNIP) and its related pathways were proved to be important molecular therapeutic targets. ,, for the reasons above, TXNIP was widely and deeply studied.
TXNIP, a multifunctional protein, which is also titled as Vitamin D3 up-regulating protein 1 or thioredoxin binding protein-2, is implicated in cell proliferation differentiation and apoptosis. Besides the central role in cancers and other stress-related diseases, ,, TXNIP is also an important regulator of glucose and lipid metabolism. , TXNIP contains two typical arrestin-like domains with PXXP or PPXY sequence, which are known as binding motif for SH3-domains containing proteins, for example trithorax (Trx), and WW-domain, for example NLRP3 respectively. ,,
Excessive reactive oxygen species (ROS) are involved in various pathological conditions.  As a main redox regulator, TXNIP negatively regulates Trx expression and its antioxidant function through combining with Trx, and such regulation is critical in the control of DNA damage and apoptosis.  In addition, ROS is the major activator of the NLRP3 inﬂammasome.  Inﬂammasomes are a group of large caspase-1-activating protein complexes in response to the resulting of innate immunity and production of pro-inﬂammatory cytokines.  Inﬂammasomes, particularly NLRP3 inﬂammasome, are shown to be activated in a series of liver diseases, including drug-induced liver injury,  viral hepatitis,  endotoxin-induced liver injury and cholestasis, , ﬁbrosis,  ischemia-reperfusion (I/R) injury,  and nonalcoholic fatty liver disease. , And many studies showed that the physical interaction between TXNIP and NLRP3 may explain the inﬂammasome activation in a ROS-sensitive manner. 
Here, we summarize the major role of TXNIP acting as a common regulation target for multiple medicines including Lycium barbarum polysaccharide (LBP), Quercetin, trans-resveratrol (T-res), Metformin, purple sweet potato color (PSPC), Nobiletin, Taurine, Suberoylanilide hydroxamic acid (SAHA), and Theophylline mediated in the clinical treatment [Table 1]. We also highlight the potential strategies used to reactivate TXNIP expression for cancer therapeutics.
|Table 1: The mechanism of various medicines regulated TXNIP related pathway|
Click here to view
| Lycium Barbarum Polysaccharide Regulates the Thioredoxin-Interacting Protein-NLRP3 Inflammasome Pathway|| |
Lycium barbarum polysaccharide (LBP) is a traditional Chinese medicine used in liver, kidney and eye diseases. , In drug-induced acute liver injury model and high-fat diet-induced NAFLD model, LBP is shown to lessen hepatic dysfunction, such as inﬂammation, oxidative stress, apoptosis, lipid deposition, and histological changes. ,
Xiao et al., have found that 50 μg/mL LBP pretreatment signiﬁcantly attenuated over-expression of TXNIP under 24-h ethanol exposure-induced, and was accompanied with the increasing of cellular apoptosis, activation of NLRP3 inﬂammasome, secretion of inﬂammatory cytokines, production of ROS, and antioxidant enzyme down expression. In addition, silence of TXNIP could inhibit NLRP3 inﬂammasome activation, promote oxidative stress and worsen apoptosis in cells. These results indicated that LBP contributes to the attenuation of cellular apoptosis, oxidative stress and inﬂammation lesions via inhibition of hepatic TXNIP-NLRP3 inﬂammasome pathway.
| Quercetin Inhibits AMP Activated Kinase/Thioredoxin-Interacting Protein Activation and Reduces Inflammatory Lesions|| |
Quercetin, a traditional therapeutic for high fructose-induced insulin resistance and hyperlipidemia, has multiple bioactivities including anti-oxidation, anti-inflammation, anti-hyperlipidemia and anti-diabetes. , Zhang et al. investigated the regulatory effects of Quercetin on the hypothalamus in high fructose-fed rats. Then they found that Quercetin inhibits AMP activated kinase (AMPK)/TXNIP and its downstream pathway of Nuclear factor-κB (NF-κB)/NLRP3 inflammasome activation in vivo. The result meant that it may be associated with the reduction of hypothalamic inflammatory lesions, benefiting to the improvement of hypothalamic insulin signaling defect in this model.
| Trans-Resveratrol Downregulates Thioredoxin-Interacting Protein Overexpression During Liver Ischemia-Reperfusion|| |
Trans-resveratrol is a well-known natural phytoalexin with anti-oxidative, anti-apoptotic and anti-proliferative effects.  In isolated perfused liver and cultured hepatocytes, T-res has been reported to possess the protective properties against oxidative stress. , Nivet-Antoine et al. studied the effects of a postischemic treatment of T-res on the liver Trx/TXNIP system. Finally, they found the liver I/R upregulated hepatic TXNIP expression. Meanwhile, T-res would suppress the over-expression of I/R TXNIP. It is obvious that the decrease of TXNIP expression by T-res was associated with an increase in liver Trx redox activity.
| Metformin Suppresses Thioredoxin-Interacting Protein Gene Expression to Maintain Glucose Homeostasis|| |
Metformin is suggested as a conventional therapeutic for type-II diabetes mellitus to control the blood sugar level.  It is reported that TXNIP plays major role in glucose metabolism through inhibiting cellular glucose uptake and metabolism, as well as enhancing hepatic gluconeogenesis. ,,
Chai et. al. demonstrated metformin significantly reduced TXNIP mRNA and protein expression in cultured cells. The main reason is that the inhibition of mitochondrial complex I and increased glycolysis are partially associated with the AMPK. Moreover, the recruiting of Mondo: MLX to the TXNIP gene promoter also decreased, indicating that the transcription of the TXNIP gene is inhibited by metformin. These observations propose that the novel action of metformin on the TXNIP gene expression may contribute to the therapeutic effects on type II diabetes treatment.
| Purple Sweet Potato Color Inhibits Oxidative Stress-Mediated Thioredoxin-Interacting Protein/NLRP3 Inflammasome Activation|| |
Inﬂammation has important effect on the pathogenesis of obesity.  PSPC was reported to have a potential anti-inﬂammation efﬁcacy.  Shan et al. showed PSPC could signiﬁcantly lessen the kidney NLRP3 inﬂammasome activation, inhibit I kappa B kinase b activation, block the nuclear translocation of NF-kB, and reduce the oxidative stress-associated AGE receptor (RAGE) and TXNIP expression level. These data implied that the advantageous roles of PSPC on high fat diet-induced kidney disorder and damage are associated with TXNIP/NLRP3 signaling pathways, providing a potential target for obesity.
| Nobiletin Downregulates Thioredoxin-Interacting Protein Expression|| |
Nobiletin, a citrus polymethoxy ﬂavonoid with six methoxy groups, was presented abundantly in the peels of citrus fruits.  Over-expression of TXNIP has recently been considered as a crucial factor for irremediable endoplasmic reticulum (ER) stress leading to the programmed cell death of pancreatic β-cell. , Ikeda et al. confirmed that nobiletin decreased both the tunicamycin-induced cellular apoptosis and the subsequent suppression of TXNIP over-expression. Therefore, it is possible that nobiletin can improve ER stress-induced neurological disorders partly via suppressing TXNIP expression. The future study for this mechanism would provide novel insights not only into nobiletin's beneﬁcial actions on various human diseases, but also into the functions of TXNIP in those diseases.
| Effect of Taurine on MRNA Expression of Thioredoxin-Interacting Protein|| |
Taurine (also titled as 2-aminoethanesulfonic acid), a sulfur-containing β-amino acid, plays significant role in numerous essential biological processes.  In order to explore the potential mechanisms for these regulatory functions, especially at the genetic level, Gondo et al. investigated the effects of taurine on the gene expression proﬁle (GEP) by means of DNA microarray in Caco-2 cells. The results showed that Taurine increased the TXNIP mRNA expression and promoter activity. However, β-alanine or c-aminobutyric acid, which structurally or functionally related to taurine, did not increase TXNIP mRNA and protein expression. The study verified the taurine-speciﬁc physiological function of TXNIP up-regulation.
| Histone Deacetylation Inhibitors Suberoylanilide Hydroxamic Acid-Mediated Repression of Thioredoxin-Interacting Protein Expression|| |
Suberoylanilide hydroxamic acid was received Food and Drug Administration approval in 2006 for the treatment of refractory cutaneous T-cell lymphoma.  Moreover, it is currently in clinical trials for acute myeloid leukemia and myelodysplastic syndromes. However, its mechanism of action is unclear. Butler et al. performed GEP of prostate cancer cell line LNCaP with SAHA treatment in a time-dependent manner. The studies proved that treatment with SAHA increased the expression of TXNIP, resulting in attenuating Trx expression and activity in cancer cells but not normal cells, switched Trx1 oxidation state toward a more oxidized one, and complex formation with Trx1. Complex formation with Trx1 further leads to the accumulation of ROS. This study indicated that one possible mechanism for the anticancer effect of SAHA is via the Trx1/TXNIP system. ,,
| Theophylline Regulates Inflammatory and Neurotrophic Factor Signals|| |
Theophylline is widely used in the clinical treatment of asthma, chronic pulmonary obstructive disease, and premature infants with respiratory deﬁcits. ,, Singh et al. provided the ﬁrst evidence that theophylline-induced respiratory recovery in the C2H model is associated with induction of both neurotrophic factors (brain derived neurotrophic factor, glial cell line-derived neurotrophic factor, and Bcl2) and pro-inﬂammatory genes (TXNIP, interleukin-1β (IL-1β), tumor necrosis factor-α and inducible nitric-oxide synthase). And the ﬁndings in this study demonstrated that the elevated levels of TXNIP/NF-κB/IL-1β pathway were in agreement with the results reported by Perrone et al., whose study demonstrated that TXNIP/NF-κB/IL-1β axis was involved in recovery of partial sciatic nerve injury and primary Schwann cell activation. Therefore, the enhanced resolution of early inﬂammatory processes and expression of pro-survival factors may be the potential treatment targets and intracellular signals underling theophylline-induced respiratory recovery.
| Conclusions and Therapeutic Implications|| |
In summary, TXNIP mediates oxidative stress via binding and inhibition of Trx, a major ROS scavenger with multifunction. Lack of TXNIP promotes cell proliferation and protects cell against apoptosis. Abundant researches and clinical studies have confirmed that TXNIP acts as a tumor suppressor in various malignancies. It appears that the cancer cells have developed multiple ways to inactivate TXNIP, indicating the importance of repression of TXNIP in tumorigenesis. As such, regulation of TXNIP expression could be a new and viable approach for epigenetic therapies through the use of either LBP, quercetin, T-res, metformin, PSPC, nobiletin, taurine, SAHA, theophylline or in combination fashion [Figure 1].
|Figure 1: TXNIP is signaling pathways and medicines functions. ⊥signs indicate inhibition and ↓signs indicate activation. LBP: Lycium barbarum polysaccharide; SAHA: Suberoylanilide hydroxamic acid; T-res: Trans-resveratrol; PSPC: Purple sweet potato color; TXNIP: Thioredoxin-interacting protein; Trx: Trithorax; ROS: Reactive oxygen species; ER: Endoplasmic reticulum|
Click here to view
Further characterizing TXNIP functions, including its role in Trx regulation, NLRP3 inﬂammasome activation, and glucose metabolism, would not only provide new insights into epigenetic repression of TXNIP in cancer biology, but also offer new therapeutic approaches to the treatment and prevention of cancer.
| References|| |
Davis FG, McCarthy BJ. Current epidemiological trends and surveillance issues in brain tumors. Expert Rev Anticancer Ther
2001; 1(3): 395 -0 401.
Kim SY, Suh HW, Chung JW, Yoon SR, Choi I. Diverse functions of VDUP1 in cell proliferation, differentiation, and diseases. Cell Mol Immunol
2007; 4(5): 345-51.
Patwari P, Chutkow WA, Cummings K, Verstraeten VLRM, Lammerding J, Schreiter ER, Lee RT. Thioredoxin-independent regulation of metabolism by the alpha-arrestin proteins. J Biol Chem
2009; 284(37): 24996-5003.
Kaimul AM, Nakamura H, Masutani H, Yodoi J. Thioredoxin and thioredoxin- binding protein-2 in cancer and metabolic syndrome. Free Radic Biol Med
2007; 43(6): 861-8.
Chutkow WA, Patwari P, Yoshioka J, Lee RT. Thioredoxin-interacting protein (Txnip) is a critical regulator of hepatic glucose production. J Biol Chem
2008; 283(4): 2397-406.
Yoshida T, Kondo N, Oka SI, Ahsan MK, Hara T, Masutani H, Nakamura H, Yodoi J. Thioredoxin-binding protein-2 (TBP-2): its potential roles in the aging process. Biofactors
2006; 27(1-4): 47-51.
Nishinaka Y, Masutani H, Oka SI, Matsuo Y, Yamaguchi Y, Nishio K, Ishii K, Yodoi J. Importin alpha1 (Rch1) mediates nuclear translocation of thioredoxin- binding protein-2/vitamin D(3)-up-regulated protein 1. J Biol Chem
Yoshihara E, Fujimoto S, Inagaki N, Okawa K, Masaki S, Yodoi J, Masutani H. Disruption of TBP-2 ameliorates insulin sensitivity and secretion without affecting obesity. Nat Commun
2010; 1: 127.
Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J. Thioredoxin-interacting protein links oxidative stress to inﬂammasome activation. Nat Immunol
2010; 11(2): 136-140.
Jaeschke H, Mechanisms of Liver Injury. II. Mechanisms of neutrophil-induced liver cell injury during hepatic ischemia-reperfusion and other acute inﬂammatory conditions. Am J Physiol Gastrointest Liver Physiol
2006; 290(6): G1083-8.
Kaimul AM, Nakamura H, Masutani H, Yodoi J. Thioredoxin and thioredoxin- binding protein-2 in cancer and metabolic syndrome. Free Radical Biol Med
2007; 43: 861-8.
Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J. Thioredoxin-interacting protein links oxidative stress to inﬂammasome activation. Nat Immunol
2010; 11(2): 136-40.
Lamkanﬁ M, Dixit VM. Inflammasomes and their roles in health and disease. Annu Rev Cell Dev Biol
2012; (28): 137-61.
Imaeda AB, Watanabe A, Sohail MA, Mahmood S, Mohamadnejad M, Sutterwala FS, Flavell RA, MehalWZ. Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome. Mehal J Clin Invest
2009; 119(2): 305-14.
Burdette D, Haskett A, Presser L, McRae S, Iqbal J, Waris G. Hepatitis C virus activates interleukin- 1beta via caspase-1-inflammasome complex. J Gen Virol
2012; 93(Pt 2): 235-46.
Bauernfeind FG, Horvath G, Stutz A, Alnemri ES, MacDonald K, Speert D, Fernandes-Alnemri T, Wu JH, Monks BG, Fitzgerald KA, Hornung V, Latz E. Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J Immunol
2009; 183(2): 787-91.
Ganz M, Csak T, Nath B, Szabo G. Lipopolysaccharide induces and activates the Nalp3 inflammasome in the liver. World J Gastroenterol
2011; 17(43): 4772-8.
Watanabe A, Sohail MA, Gomes DA, Hashmi A, Nagata J, Sutterwala FS, Mahmood S, Jhandier MN, Shi Y, Flavell RA, Mehal1 WZ. Inflammasome-mediated regulation of hepatic stellate cells. Am J Physiol Gastrointest Liver Physiol
2009; 296(6): G1248-57.
Takeuchi D, Yoshidome H, Kato A, Ito H, Kimura F, Shimizu H, Ohtsuka M, Morita Y, Miyazaki M. Interneukin18 causes hepatic ischemia/ reperfusion injury by anti-inflammatory cytokinr expression in mice. Hepatology
2004; 39(3): 699-710.
Csak T, Ganz M, Pespisa J, Kodys K, Dolganiuc A, Szabo G. Fatty acid and endotoxin activate inflammasom that release danger signals to stimulate immune cells. Hepatology
2011; 54(1): 133-44.
Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Mynatt RL, Ravussin E, Stephens JM, Dixit VD. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med
2011; 17(2): 179-88.
Li H, Liang Y, Chiu K, Yuan QJ, Lin B, Chang RCC, So KF. Lycium barbarum (wolfberry) reduces secondary degeneration and oxidative stress, and inhibits JNK pathway in retina after partial optic nerve transection. PLoS One
2013; 8(7): e68881.
Xiao J, Liong EC, Ching YP, Chang RCC, So KF, Fung ML, Tipoe GL. Lycium barbarum polysaccharides protect mice liver from carbon tetrachloride-induced oxidative stress and necroinflammation. J Ethnopharmacol
2012; 139(2): 462-70.
Xiao J, Liong EC, Ching YP, Chang RCC, Fung ML, Xu AM, So KF, Tipoe GL. Lycium barbarum polysaccharides protect rat liver from non-alcoholic steatohepatitis-induced injury. Nutr Diab
2013; (3): e81.
Xiao J, Zhu YH, Liu YX, Tipoe GL, Xing FY, So KF. Lycium barbarum polysaccharide attenuates alcoholic cellular injury through TXNIP-NLRP3 inﬂammasome pathway. Int J Biol Macromol
2014; (69): 73-8.
Bischoff SC. Quercetin: potentials in the prevention and therapy of disease. Curr Opin Clin Nutr Metab Car
2008; 11(6): 733-40.
Russo M, Spagnuolo C, Tedesco I, Bilotto S, Russo GL. The flavonoid quercetin in disease prevention and therapy: facts and fancies. Biochem Pharmacol
2012; 83(1): 6-15.
Zhang QY, Pan Y, Wang R, Kang LL, Xue QC, Wang XN, Kong LD. Quercetin inhibits AMPK/TXNIP activation and reduces inflammatory lesions to improve insulin signaling defect in the hypothalamus of high fructose-fed rats. J Nutr Biochem
2014; 25(4): 420-8.
Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov
2006; 5(6): 493-506.
Plin C, Tillement JP, Berdeaux A, Morin D. Resveratrol protects against cold ischemia-warm reoxygenation-induced damages to mitochondria and cells in rat liver. Eur J Pharmacol
2005; 528(1): 162-8.
Notas G, Niﬂi AP, Kampa M, Vercauteren J, Kouroumalis E, Castanas E. Resveratrol exerts its antiproliferative effect on HepG2 hepatocellular carcinoma cells, by inducing cell cycle arrest, and NOS activation. Biochim Biophys Acta
2006; 1760(11): 1657-66.
Nivet-Antoine V, Cottart CH, Lemaréchal H, Vamy M, Margaill I, Beaudeux JL, Bonnefont-Rousselot D, Borderie D. trans-Resveratrol down regulates Txnip over- expression occurring during liver ischemia-reperfusion. Biochimi
2010; 92(12): 1766-71.
Kirpichnikov D, McFarlane SI, Sowers JR. Metformin: an update. Annals Int Med
2002; 137(1): 25-33.
Donnelly KL, Margosian MR, Sheth SS, Lusis AJ, Parks EJ. Increased lipogenesis and Fatty Acid reesterification contribute to hepatic triacylglycerol stores in hyperlipidemic txnip(-/-) mice. J Nutr
2004; 134(6): 1475-80.
Oka S, Liu W, Masutani H, Hirata H, Shinkai Y, Yamada SI, Yoshida T, Nakamura H, Yodoi J. Impaired fatty acid utilization in thioredoxin binding protein-2 (TBP-2)-deficient mice. A unique animal model of Reye syndrome. FASEB J
2006; 20(1): 121-3.
Parikh H, Carlsson E, Chutkow WA, Johansson LE, Storgaard H, Poulsen P, Saxena R, Ladd C, Schulze PC, Mazzini MJ, Jensen CB, Krook A, Björnholm M, Tornqvist H, Zierath JR, Ridderstråle M, Altshuler D, Lee RT, Vaag A, Groop LC, Mootha VK. TXNIP Regulates Peripheral Glucose Metabolism in Humans. PLoS Med
2007; 4(5): e158.
Chai TF, Hong SY, He HP, Zheng LL, Hagen T, Luo Y, Yu FX. A potential mechanism of metformin-mediated regulation of glucose homeostasis: inhibition of Thioredoxin- interacting protein (Txnip) gene expression. Cell Signal
2012; 24(8): 1700-5
Dong H, Huang H, Yun X, Kim DS, Yue YN, Wu HJ, Sutter A, Chavin KD, Otterbein LE, Adams DB, Kim YB, Wang HJ. Bilirubin increases insulin sensitivity in leptin-receptor deﬁcient and diet-induced obese mice through suppression of ER stress and chronic inﬂammation. Endocrinology
2014; 155(3): 818-28 .
Kano M, Takayanagi T, Harada, Makino K, Ishikawa F. Antioxidative activity of anthocyanins from purple sweet potato, Ipomoera batatas cultivarAyamurasa ki. Biosci Biotechnol Biochem
2005; 69(5): 979-88.
Shan Q, Zheng YL, Lu J, Zhang ZF, Wu DM, Fan SH, Hu B, Cai XJ, Cai H, Liu PL, Liu F. Purple sweet potato color ameliorates kidney damage via inhibiting oxidative stress mediated NLRP3 inﬂammasome activation in high fat diet mice. Food Chem Toxicol
2014; (69): 339-46.
Oda T, Kosuge Y, Arakawa M, Ishige K, Ito Y. Distinct mechanism of cell death is responsible for tunicamycin-induced ER stress in SK-N-SH and SH-SY5Y cells. Neurosci Res
2008; 60(1): 29-39.
Anthony TG, Wek RC, TXNIP switches tracks toward a terminal UPR. Cell Metab
2012; 16(2): 135-7.
Oslowski CM, Hara T, Sullivan-Murphy BO, Kanekura K, Lu S, Hara M, Ishigaki S, Zhu LJ, Hayashi E, Hui ST, Greiner D, Kaufman RJ, Bortell R, Urano F. Thioredoxin-interacting protein mediates ER stress-induced β-cell death through initiation of the inﬂammasome. Cell Metab
2012; 16(2): 265-73.
Ikedaa A, Nemotoa K, Yoshida C, Miyata S, Mori J, Soejima S, Yokosuka A, Mimaki Y, Ohizumi Y, Degawa M, Nemoto K. Suppressive effect of nobiletin, a citrus polymethoxyﬂavonoid that downregulates thioredoxin-interacting protein expression, on tunicamycin-induced apoptosis in SK-N-SH human neuroblastoma cells. Neurosci Lett
2013; (549): 135-9.
Huxtable RJ. Physiological actions of taurine. Physiol Rev
1992; 72(1): 101-63
Gondo Y, Satsu H, Ishimoto Y, Iwamoto T, Shimizu M. Effect of taurine on mRNA expression of thioredoxin interacting protein in Caco-2 cells. Biochem Bioph Res Co
2012; 426(3): 433-7.
Zhou JB, Yu Q, Chng WJ. TXNIP (VDUP-1, TBP-2): A major redox regulator commonly suppressed in cancer by epigenetic mechanisms. Int J Biochem Cell B
2011; 43(12): 1668-73.
Butler LM, Zhou X, Xu WS, Scher HI, Rifkind RA, Marks PA, Richon VM. The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin. Proc Natl Acad Sci
2002; 99(18): 11700-5.
Ungerstedt JS, Sowa Y, Xu WS, Shao Y, Dokmanovic M, Perez G, Ngo L, Holmgren A, Jiang X, Marks PA . Role of thioredoxin in the response of normal and transformed cells to histone deacetylase inhibitors. Proc Natl Acad Sci
2005; 102(3): 673-8.
Ungerstedt J, Du Y, Zhang H, Nair D, Holmgren A. In vivo redox state of Human thioredoxin and redox shift by the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA). Free Radical Bio Med
2012; (53): 2002-7.
Nantwi KD, Goshgarian HG, Theophylline-induced recovery in a hemidiaphragm paralyzed by hemisection in rats. Contribution of adenosine receptors. Neuropharmacology
1998; 37(1): 113-21.
Nantwi KD, Goshgarian HG. Effects of chronic theophylline injections on recovery of hemidiaphragmatic function after cervical spinal cord injury in rats. Brain Res
1998; 789(1): 126-9.
Nantwi KD, El-Bohy AA, Goshgarian HG. Actions of systematic theophylline on hemidiaphragm recovery in rats following cervical spinal cord hemisection. Exp Neurol
1996; 140(1): 53-9.
Singh LP, Devi TS, Nantwi KD. Theophylline regulates inﬂammatory and neurotrophic factor signals in functional recovery after C2-hemisection in adult rats. Exp Neurol
2012; 238(1): 79-88.
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.