Login Register Cart 0
Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Research Article

Implication of Thioredoxin 1 and Glutaredoxin 1 in H2O2-induced Phosphorylation of JNK and p38 MAP Kinases

Author(s): Efthymios Poulios*, Vasiliki Roupaka, Constantinos Giaginis, Dimitrios Galaris and Giannis Spyrou*

Volume 25, Issue 3, 2025

Published on: 12 January, 2024

Page: [305 - 319] Pages: 15

DOI: 10.2174/0115665240271103231127072635

Price: $65

Abstract

Background. Aerobic organisms continuously generate small amounts of Reactive Oxygen Species (ROS), which are involved in the oxidation of sensitive cysteine residues in proteins, leading to the formation of disulfide bonds. Thioredoxin (Trx1) and Glutaredoxin (Grx1) represent key antioxidant enzymes reducing disulfide bonds.

Objective. In this work, we have focused on the possible protective effect of Trx1 and Grx1 against oxidative stress-induced DNA damage and apoptosis-signaling, by studying the phosphorylation of MAP kinases.

Methods. Trx1 and Grx1 were overexpressed or silenced in cultured H1299 non-small cell lung cancer epithelial cells. We examined cell growth, DNA damage, and the phosphorylation status of MAP kinases following treatment with H2O2.

Results. Overexpression of both Trx1 and Grx1 had a significant impact on the growth of H1299 cells and provided protection against H2O2-induced toxicity, as well as acute DNA single-strand breaks. Conversely, silencing of these proteins exacerbated DNA damage. Furthermore, overexpression of Trx1 and Grx1 inhibited the rapid phosphorylation of JNK (especially at 360 min of treatment, ****p=0.004 and **p=0.0033 respectively) and p38 MAP kinases (especially at 360 min of treatment, ****p<0.0001 and ***p=0.0008 respectively) during H2O2 exposure, while their silencing had the opposite effect (especially at 360 min of treatment, ****p<0.0001).

Conclusion. These results suggest that both Trx1 and Grx1 have protective roles against H2O2 induced toxicity, emphasizing their significance in mitigating oxidative stress-related cellular damage.

Keywords: Thioredoxin, glutaredoxin, JNK, hydrogen peroxide, redox signaling, MAPKs.

« Previous Next »
[1]
Jena AB, Samal RR, Bhol NK, Duttaroy AK. Cellular Red-Ox system in health and disease: The latest update. Biomed Pharmacother 2023; 162: 114606.
[http://dx.doi.org/10.1016/j.biopha.2023.114606] [PMID: 36989716]
[2]
Zuo J, Zhang Z, Luo M, et al. Redox signaling at the crossroads of human health and disease. MedComm 2022; 3(2): e127.
[3]
Mailloux RJ. An Update on Mitochondrial Reactive Oxygen Species Production. Antioxidants 2020; 9(6): 472.
[http://dx.doi.org/10.3390/antiox9060472] [PMID: 32498250]
[4]
Ray PD, Huang BW, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal 2012; 24(5): 981-90.
[http://dx.doi.org/10.1016/j.cellsig.2012.01.008] [PMID: 22286106]
[5]
Ji LL, Yeo D. Oxidative stress: An evolving definition. Fac Rev 2021; 10: 13.
[http://dx.doi.org/10.12703/r/10-13] [PMID: 33659931]
[6]
McCord JM. The evolution of free radicals and oxidative stress. Am J Med 2000; 108(8): 652-9.
[http://dx.doi.org/10.1016/S0002-9343(00)00412-5] [PMID: 10856414]
[7]
Juan CA, Pérez de la Lastra JM, Plou FJ, Pérez-Lebeña E. The chemistry of reactive oxygen species (ROS) Revisited: outlining their role in biological macromolecules (DNA, lipids and proteins) and induced pathologies. Int J Mol Sci 2021; 22(9): 4642.
[http://dx.doi.org/10.3390/ijms22094642] [PMID: 33924958]
[8]
Benhar M. Oxidants, antioxidants and thiol redox switches in the control of regulated cell death pathways. Antioxidants 2020; 9(4): 309.
[http://dx.doi.org/10.3390/antiox9040309] [PMID: 32290499]
[9]
Burgoyne JR, Oka S, Ale-Agha N, Eaton P. Hydrogen peroxide sensing and signaling by protein kinases in the cardiovascular system. Antioxid Redox Signal 2013; 18(9): 1042-52.
[http://dx.doi.org/10.1089/ars.2012.4817] [PMID: 22867279]
[10]
Stone JR, Yang S. Hydrogen peroxide: A signaling messenger. Antioxid Redox Signal 2006; 8(3-4): 243-70.
[http://dx.doi.org/10.1089/ars.2006.8.243] [PMID: 16677071]
[11]
Vašková J, Kočan L, Vaško L, Perjési P. Glutathione-Related Enzymes and Proteins: A Review. Molecules 2023; 28(3): 1447.
[http://dx.doi.org/10.3390/molecules28031447] [PMID: 36771108]
[12]
Kukulage DSK, Matarage Don NNJ, Ahn YH. Emerging chemistry and biology in protein glutathionylation. Curr Opin Chem Biol 2022; 71: 102221.
[http://dx.doi.org/10.1016/j.cbpa.2022.102221] [PMID: 36223700]
[13]
Kalinina E, Novichkova M. Glutathione in protein redox modulation through S-glutathionylation and S-nitrosylation. Molecules 2021; 26(2): 435.
[http://dx.doi.org/10.3390/molecules26020435] [PMID: 33467703]
[14]
Ghezzi P. Protein glutathionylation in health and disease. Biochim Biophys Acta, Gen Subj 2013; 1830(5): 3165-72.
[http://dx.doi.org/10.1016/j.bbagen.2013.02.009] [PMID: 23416063]
[15]
Mieyal JJ, Gallogly MM, Qanungo S, Sabens EA, Shelton MD. Molecular mechanisms and clinical implications of reversible protein S-glutathionylation. Antioxid Redox Signal 2008; 10(11): 1941-88.
[http://dx.doi.org/10.1089/ars.2008.2089] [PMID: 18774901]
[16]
Gallogly MM, Mieyal JJ. Mechanisms of reversible protein glutathionylation in redox signaling and oxidative stress. Curr Opin Pharmacol 2007; 7(4): 381-91.
[http://dx.doi.org/10.1016/j.coph.2007.06.003] [PMID: 17662654]
[17]
Hanschmann EM, Godoy JR, Berndt C, Hudemann C, Lillig CH. Thioredoxins, glutaredoxins, and peroxiredoxins--molecular mechanisms and health significance: From cofactors to antioxidants to redox signaling. Antioxid Redox Signal 2013; 19(13): 1539-605.
[http://dx.doi.org/10.1089/ars.2012.4599] [PMID: 23397885]
[18]
Michelet L, Zaffagnini M, Massot V, et al. Thioredoxins, glutaredoxins, and glutathionylation: New crosstalks to explore. Photosynth Res 2006; 89(2-3): 225-45.
[http://dx.doi.org/10.1007/s11120-006-9096-2] [PMID: 17089213]
[19]
Holmgren A. Thioredoxin and glutaredoxin systems. J Biol Chem 1989; 264(24): 13963-6.
[http://dx.doi.org/10.1016/S0021-9258(18)71625-6] [PMID: 2668278]
[20]
Xinastle-Castillo LO, Landa A. Physiological and modulatory role of thioredoxins in the cellular function. Open Med (Wars) 2022; 17(1): 2021-35.
[http://dx.doi.org/10.1515/med-2022-0596] [PMID: 36568514]
[21]
Hasan AA, Kalinina E, Tatarskiy V, Shtil A. The thioredoxin system of mammalian cells and its modulators. Biomedicines 2022; 10(7): 1757.
[http://dx.doi.org/10.3390/biomedicines10071757] [PMID: 35885063]
[22]
Lu J, Holmgren A. The thioredoxin antioxidant system. Free Radic Biol Med 2014; 66: 75-87.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.07.036] [PMID: 23899494]
[23]
Lee S, Kim SM, Lee RT. Thioredoxin and thioredoxin target proteins: From molecular mechanisms to functional significance. Antioxid Redox Signal 2013; 18(10): 1165-207.
[http://dx.doi.org/10.1089/ars.2011.4322] [PMID: 22607099]
[24]
Ogata FT, Branco V, Vale FF, Coppo L. Glutaredoxin: Discovery, redox defense and much more. Redox Biol 2021; 43: 101975.
[http://dx.doi.org/10.1016/j.redox.2021.101975] [PMID: 33932870]
[25]
Matsui R, Ferran B, Oh A, et al. Redox regulation via glutaredoxin-1 and protein S-glutathionylation. Antioxid Redox Signal 2020; 32(10): 677-700.
[http://dx.doi.org/10.1089/ars.2019.7963] [PMID: 31813265]
[26]
Yue J, López JM. Understanding MAPK signaling pathways in apoptosis. Int J Mol Sci 2020; 21(7): 2346.
[http://dx.doi.org/10.3390/ijms21072346] [PMID: 32231094]
[27]
Sun Y, Liu WZ, Liu T, Feng X, Yang N, Zhou HF. Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis. J Recept Signal Transduct Res 2015; 35(6): 600-4.
[http://dx.doi.org/10.3109/10799893.2015.1030412] [PMID: 26096166]
[28]
Kim EK, Choi EJ. Compromised MAPK signaling in human diseases: An update. Arch Toxicol 2015; 89(6): 867-82.
[http://dx.doi.org/10.1007/s00204-015-1472-2] [PMID: 25690731]
[29]
Peti W, Page R. Molecular basis of MAP kinase regulation. Protein Sci 2013; 22(12): 1698-710.
[http://dx.doi.org/10.1002/pro.2374] [PMID: 24115095]
[30]
Morrison DK. Cold Spring Harb Perspect Biol 2012; 4.
[31]
Cargnello M, Roux PP. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev 2011; 75(1): 50-83.
[http://dx.doi.org/10.1128/MMBR.00031-10] [PMID: 21372320]
[32]
Takekawa M, Kubota Y, Nakamura T, Ichikawa K. Regulation of stress-activated MAP kinase pathways during cell fate decisions. Nagoya J Med Sci 2011; 73(1-2): 1-14.
[PMID: 21614932]
[33]
Cuadrado A, Nebreda AR. Mechanisms and functions of p38 MAPK signalling. Biochem J 2010; 429(3): 403-17.
[http://dx.doi.org/10.1042/BJ20100323] [PMID: 20626350]
[34]
Kim EK, Choi EJ. Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta Mol Basis Dis 2010; 1802(4): 396-405.
[http://dx.doi.org/10.1016/j.bbadis.2009.12.009] [PMID: 20079433]
[35]
Tobiume K, Matsuzawa A, Takahashi T, et al. ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis. EMBO Rep 2001; 2(3): 222-8.
[http://dx.doi.org/10.1093/embo-reports/kve046] [PMID: 11266364]
[36]
Obsil T, Obsilova V. Structural aspects of protein kinase ASK1 regulation. Adv Biol Regul 2017; 66: 31-6.
[http://dx.doi.org/10.1016/j.jbior.2017.10.002] [PMID: 29066278]
[37]
Shiizaki S, Naguro I, Ichijo H. Activation mechanisms of ASK1 in response to various stresses and its significance in intracellular signaling. Adv Biol Regul 2013; 53(1): 135-44.
[http://dx.doi.org/10.1016/j.jbior.2012.09.006] [PMID: 23031789]
[38]
Soga M, Matsuzawa A, Ichijo H. Oxidative stress-induced diseases via the ASK1 signaling pathway. Int J Cell Biol 2012; 2012: 1-5.
[http://dx.doi.org/10.1155/2012/439587] [PMID: 22654913]
[39]
Matsuzawa A, Ichijo H. Biochim Biophys Acta 2008; 1780: 13251336.
[40]
Fujino G, Noguchi T, Takeda K, Ichijo H. Thioredoxin and protein kinases in redox signaling. Semin Cancer Biol 2006; 16(6): 427-35.
[http://dx.doi.org/10.1016/j.semcancer.2006.09.003] [PMID: 17081769]
[41]
Allen EMG, Mieyal JJ. Protein-thiol oxidation and cell death: Regulatory role of glutaredoxins. Antioxid Redox Signal 2012; 17(12): 1748-63.
[http://dx.doi.org/10.1089/ars.2012.4644] [PMID: 22530666]
[42]
Koufaki M, Theodorou E, Galaris D, Nousis L, Katsanou ES, Alexis MN. Chroman/catechol hybrids: Synthesis and evaluation of their activity against oxidative stress induced cellular damage. J Med Chem 2006; 49(1): 300-6.
[http://dx.doi.org/10.1021/jm0506120] [PMID: 16392814]
[43]
Barbouti A, Doulias PT, Nousis L, Tenopoulou M, Galaris D. DNA damage and apoptosis in hydrogen peroxide-exposed Jurkat cells: Bolus addition versus continuous generation of H2O2. Free Radic Biol Med 2002; 33(5): 691-702.
[http://dx.doi.org/10.1016/S0891-5849(02)00967-X] [PMID: 12208356]
[44]
Kitsati N, Mantzaris MD, Galaris D. Hydroxytyrosol inhibits hydrogen peroxide-induced apoptotic signaling via labile iron chelation. Redox Biol 2016; 10: 233-42.
[http://dx.doi.org/10.1016/j.redox.2016.10.006] [PMID: 27810738]
[45]
Mantzaris MD, Bellou S, Skiada V, Kitsati N, Fotsis T, Galaris D. Intracellular labile iron determines H 2 O 2 -induced apoptotic signaling via sustained activation of ASK1/JNK-p38 axis. Free Radic Biol Med 2016; 97: 454-65.
[http://dx.doi.org/10.1016/j.freeradbiomed.2016.07.002] [PMID: 27387771]
[46]
Song JS, Cho HH, Lee BJ, Bae YC, Jung JS. Role of thioredoxin 1 and thioredoxin 2 on proliferation of human adipose tissue-derived mesenchymal stem cells. Stem Cells Dev 2011; 20(9): 1529-37.
[http://dx.doi.org/10.1089/scd.2010.0364] [PMID: 21158569]
[47]
Park WH. Upregulated thioredoxin and its reductase prevent H2O2-induced growth inhibition and death in human pulmonary artery smooth muscle cells. Toxicol In Vitro 2019; 61: 104590.
[http://dx.doi.org/10.1016/j.tiv.2019.104590] [PMID: 31279089]
[48]
Park WH. Upregulation of thioredoxin and its reductase attenuates arsenic trioxide induced growth suppression in human pulmonary artery smooth muscle cells by reducing oxidative stress. Oncol Rep 2020; 43(1): 358-67.
[PMID: 31789420]
[49]
Chen B, Nelin VE, Locy ML, Jin Y, Tipple TE. Thioredoxin-1 mediates hypoxia-induced pulmonary artery smooth muscle cell proliferation. Am J Physiol Lung Cell Mol Physiol 2013; 305(5): L389-95.
[http://dx.doi.org/10.1152/ajplung.00432.2012] [PMID: 23812635]
[50]
Mochizuki M, Kwon YW, Yodoi J, Masutani H. Thioredoxin regulates cell cycle via the ERK1/2-cyclin D1 pathway. Antioxid Redox Signal 2009; 11(12): 2957-71.
[http://dx.doi.org/10.1089/ars.2009.2623] [PMID: 19622016]
[51]
El Feky S, Megahed M, Abd El Moneim N, Zaher E, Khamis S, Ali L. Cytotoxic, chemosensitizing and radiosensitizing effects of curcumin based on thioredoxin system inhibition in breast cancer cells: 2D vs. 3D cell culture system. Exp Ther Med 2021; 21(5): 506.
[http://dx.doi.org/10.3892/etm.2021.9937] [PMID: 33791015]
[52]
Wei X, Zeng Y, Meng F, et al. Calycosin-7-glucoside promotes mitochondria-mediated apoptosis in hepatocellular carcinoma by targeting thioredoxin 1 to regulate oxidative stress. Chem Biol Interact 2023; 374: 110411.
[http://dx.doi.org/10.1016/j.cbi.2023.110411] [PMID: 36812960]
[53]
Jabbar S, Mathews P, Wang X, et al. Thioredoxin-1 regulates self-renewal and differentiation of murine hematopoietic stem cells through p53 tumor suppressor. Exp Hematol Oncol 2022; 11(1): 83.
[http://dx.doi.org/10.1186/s40164-022-00329-3] [PMID: 36316713]
[54]
Liu X, Jann J, Xavier C, Wu H. Glutaredoxin 1 (Grx1) protects human retinal pigment epithelial cells from oxidative damage by preventing AKT glutathionylation. Invest Ophthalmol Vis Sci 2015; 56(5): 2821-32.
[http://dx.doi.org/10.1167/iovs.14-15876] [PMID: 25788646]
[55]
Yang F, Yi M, Liu Y, Wang Q, Hu Y, Deng H. Glutaredoxin-1 silencing induces cell senescence via p53/p21/p16 signaling axis. J Proteome Res 2018; 17(3): 1091-100.
[http://dx.doi.org/10.1021/acs.jproteome.7b00761] [PMID: 29356545]
[56]
Hanschmann EM, Wilms C, Falk L, et al. Cytosolic glutaredoxin 1 is upregulated in AMD and controls retinal pigment epithelial cells proliferation via β-catenin. Biochem Biophys Res Commun 2022; 618: 24-9.
[http://dx.doi.org/10.1016/j.bbrc.2022.06.030] [PMID: 35714567]
[57]
Peña CAP, González R, López-Grueso MJ, Antonio Bárcena J. Redox regulation of metabolic and signaling pathways by thioredoxin and glutaredoxin in nitric oxide treated hepatoblastoma cells. Redox Biol 2015; 5: 418.
[http://dx.doi.org/10.1016/j.redox.2015.09.025] [PMID: 28162284]
[58]
Fan Q, Li D, Zhao Z, Jiang Y, Lu Y. Protective effect of Glutaredoxin 1 against oxidative stress in lens epithelial cells of age-related nuclear cataracts. Mol Vis 2022; 28: 70-82.
[PMID: 35693421]
[59]
Qiu Z, Li X, Duan C, Li R, Han L. Glutaredoxin 1 protects neurons from oxygen‐glucose deprivation/reoxygenation (OGD/R)-induced apoptosis and oxidative stress via the modulation of GSK-3β/Nrf2 signaling. J Bioenerg Biomembr 2021; 53(4): 369-79.
[http://dx.doi.org/10.1007/s10863-021-09898-0] [PMID: 33956252]
[60]
Lipiński P, Drapier JC, Oliveira L, Retmańska H, Sochanowicz B, Kruszewski M. Intracellular iron status as a hallmark of mammalian cell susceptibility to oxidative stress: A study of L5178Y mouse lymphoma cell lines differentially sensitive to H2O2. Blood 2000; 95(9): 2960-6.
[http://dx.doi.org/10.1182/blood.V95.9.2960.009k13_2960_2966] [PMID: 10779446]
[61]
Chevion M. A site-specific mechanism for free radical induced biological damage: The essential role of redox-active transition metals. Free Radic Biol Med 1988; 5(1): 27-37.
[http://dx.doi.org/10.1016/0891-5849(88)90059-7] [PMID: 3075945]
[62]
Shelar SB, Kaminska KK, Reddy SA, et al. Thioredoxin-dependent regulation of AIF-mediated DNA damage. Free Radic Biol Med 2015; 87: 125-36.
[http://dx.doi.org/10.1016/j.freeradbiomed.2015.06.029] [PMID: 26119781]
[63]
Oberacker T, Fritz P, Schanz M, Alscher MD, Ketteler M, Schricker S. Enhanced Oxidative DNA-Damage in Peritoneal Dialysis Patients via the TXNIP/TRX Axis. Antioxidants 2022; 11(6): 1124.
[http://dx.doi.org/10.3390/antiox11061124] [PMID: 35740021]
[64]
Son Y, Cheong YK, Kim NH, Chung HT, Kang DG, Pae HO. Mitogen-Activated Protein Kinases and Reactive Oxygen Species: How Can ROS Activate MAPK Pathways? J Signal Transduct 2011; 2011: 1-6.
[http://dx.doi.org/10.1155/2011/792639] [PMID: 21637379]
[65]
Raman M, Chen W, Cobb MH. Differential regulation and properties of MAPKs. Oncogene 2007; 26(22): 3100-12.
[http://dx.doi.org/10.1038/sj.onc.1210392] [PMID: 17496909]
[66]
Ma YH, Su N, Chao XD, et al. Thioredoxin-1 attenuates post-ischemic neuronal apoptosis via reducing oxidative/nitrative stress. Neurochem Int 2012; 60(5): 475-83.
[http://dx.doi.org/10.1016/j.neuint.2012.01.029] [PMID: 22330043]
[67]
Yang H, Li L, Jiao Y, et al. Thioredoxin-1 mediates neuroprotection of Schisanhenol against MPP+-induced apoptosis via suppression of ASK1-P38-NF-κB pathway in SH-SY5Y cells. Sci Rep 2021; 11(1): 21604.
[http://dx.doi.org/10.1038/s41598-021-01000-3] [PMID: 34732784]
[68]
Pan D, Li W, Miao H, et al. LW-214, a newly synthesized flavonoid, induces intrinsic apoptosis pathway by down-regulating Trx-1 in MCF-7 human breast cells. Biochem Pharmacol 2014; 87(4): 598-610.
[http://dx.doi.org/10.1016/j.bcp.2013.12.010] [PMID: 24374359]
[69]
Jin R, Gao Y, Zhang S, et al. Trx1/TrxR1 system regulates post‐selected DP thymocytes survival by modulating ASK1‐JNK/p38 MAPK activities. Immunol Cell Biol 2015; 93(8): 744-52.
[http://dx.doi.org/10.1038/icb.2015.36] [PMID: 25753394]
[70]
Zeng XS, Jia JJ, Kwon Y, Wang SD, Bai J. The role of thioredoxin-1 in suppression of endoplasmic reticulum stress in Parkinson disease. Free Radic Biol Med 2014; 67: 10-8.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.10.013] [PMID: 24140863]
[71]
Cohen-Kutner M, Khomsky L, Trus M, et al. Thioredoxin-mimetic peptides (TXM) reverse auranofin induced apoptosis and restore insulin secretion in insulinoma cells. Biochem Pharmacol 2013; 85(7): 977-90.
[http://dx.doi.org/10.1016/j.bcp.2013.01.003] [PMID: 23327993]
[72]
Cohen-Kutner M, Khomsky L, Trus M, et al. Thioredoxin-mimetic peptide CB3 lowers MAPKinase activity in the Zucker rat brain. Redox Biol 2014; 2: 447-56.
[http://dx.doi.org/10.1016/j.redox.2013.12.018] [PMID: 24624334]
[73]
Wu X, Li L, Zhang L, et al. Inhibition of thioredoxin-1 with siRNA exacerbates apoptosis by activating the ASK1-JNK/p38 pathway in brain of a stroke model rats. Brain Res 2015; 1599: 20-31.
[http://dx.doi.org/10.1016/j.brainres.2014.12.033] [PMID: 25541364]
[74]
Huh KH, Cho Y, Kim BS, et al. The role of thioredoxin 1 in the mycophenolic acid-induced apoptosis of insulin-producing cells. Cell Death Dis 2013; 4(7): e721.
[http://dx.doi.org/10.1038/cddis.2013.247] [PMID: 23846223]
[75]
Ren X, Ma H, Qiu Y, et al. The downregulation of thioredoxin accelerated Neuro2a cell apoptosis induced by advanced glycation end product via activating several pathways. Neurochem Int 2015; 87: 128-35.
[http://dx.doi.org/10.1016/j.neuint.2015.06.009] [PMID: 26142569]
[76]
Song JJ, Rhee JG, Suntharalingam M, Walsh SA, Spitz DR, Lee YJ. Role of glutaredoxin in metabolic oxidative stress. Glutaredoxin as a sensor of oxidative stress mediated by H2O2. J Biol Chem 2002; 277(48): 46566-75.
[http://dx.doi.org/10.1074/jbc.M206826200] [PMID: 12244106]
[77]
Li S, Sun Y, Qi X, et al. Protective effect and mechanism of glutaredoxin 1 on coronary arteries endothelial cells damage induced by high glucose. Biomed Mater Eng 2014; 24(6): 3897-903.
[http://dx.doi.org/10.3233/BME-141221] [PMID: 25227108]
[78]
Liu X, Xavier C, Jann J, Wu H. Salvianolic acid B (Sal B) protects retinal pigment epithelial cells from oxidative stress-induced cell death by activating glutaredoxin 1 (Grx1). Int J Mol Sci 2016; 17(11): 1835.
[http://dx.doi.org/10.3390/ijms17111835] [PMID: 27827892]
[79]
Lekli I, Mukherjee S, Ray D, et al. Functional recovery of diabetic mouse hearts by glutaredoxin-1 gene therapy: Role of Akt-FoxO-signaling network. Gene Ther 2010; 17(4): 478-85.
[http://dx.doi.org/10.1038/gt.2010.9] [PMID: 20182516]
[80]
Choi YJ, Kim DW, Shin MJ, et al. PEP-1-GLRX1 reduces dopaminergic neuronal cell loss by modulating MAPK and apoptosis signaling in Parkinson’s disease. Molecules 2021; 26(11): 3329.
[http://dx.doi.org/10.3390/molecules26113329] [PMID: 34206041]
[81]
Gallogly MM, Shelton MD, Qanungo S, et al. Glutaredoxin regulates apoptosis in cardiomyocytes via NFkappaB targets Bcl-2 and Bcl-xL: Implications for cardiac aging. Antioxid Redox Signal 2010; 12(12): 1339-53.
[http://dx.doi.org/10.1089/ars.2009.2791] [PMID: 19938943]

Rights & Permissions Print Cite
Article Metrics
23
2
Wayfinder Image
© 2025 Bentham Science Publishers | Privacy Policy