NRF2 and Thioredoxin Reductase 1 as Modulators of Interactions between Zinc and Selenium
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture and Generation of Stable Knockdown Cells
2.2. Preparation of Cell Lysates
2.3. Cell Viability Assay
2.4. Measurement of Trace Element Concentrations
2.5. Enzyme Activities
2.6. Western Blot
2.7. Quantitative Real-Time PCR
2.8. Statistics
3. Results
3.1. Zinc Increased the Selenium Concentration of Cells
3.2. Thioredoxin Reductase 1 Expression Was Increased upon Zinc Treatment
3.3. Zinc Activated the Transcription Factors NRF2 and MTF1 and Enhanced the mRNA Expression of Their Target Genes
3.4. Zinc-Induced Effects on TXNRD1 and the Selenium Content Were Mediated by NRF2
3.5. Trace Element Transport Proteins Were Increased by Zinc
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
- Baudry, J.; Kopp, J.F.; Boeing, H.; Kipp, A.P.; Schwerdtle, T.; Schulze, M.B. Changes of trace element status during aging: Results of the EPIC-Potsdam cohort study. Eur. J. Nutr. 2020, 59, 3045–3058. [Google Scholar] [CrossRef] [PubMed]
- Mertens, K.; Lowes, D.A.; Webster, N.R.; Talib, J.; Hall, L.; Davies, M.J.; Beattie, J.H.; Galley, H.F. Low zinc and selenium concentrations in sepsis are associated with oxidative damage and inflammation. Br. J. Anaesth. 2015, 114, 990–999. [Google Scholar] [CrossRef] [PubMed]
- Wessells, K.R.; Brown, K.H. Estimating the global prevalence of zinc deficiency: Results based on zinc availability in national food supplies and the prevalence of stunting. PLoS ONE 2012, 7, e50568. [Google Scholar] [CrossRef] [PubMed]
- Peters, K.M.; Galinn, S.E.; Tsuji, P.A. Selenium: Dietary Sources, Human Nutritional Requirements and Intake across Populations. In Selenium: Its Molecular Biology and Role in Human Health; Hatfield, D., Schweizer, U., Tsuji, P., Gladyshev, V., Eds.; Springer International Publishing: Cham, Switzerland, 2016; pp. 295–305. [Google Scholar]
- Kryukov, G.V.; Castellano, S.; Novoselov, S.V.; Lobanov, A.V.; Zehtab, O.; Guigó, R.; Gladyshev, V.N. Characterization of mammalian selenoproteomes. Science 2003, 300, 1439–1443. [Google Scholar] [CrossRef]
- Arnér, E.S. Selenoproteins—What unique properties can arise with selenocysteine in place of cysteine? Exp. Cell Res. 2010, 316, 1296–1303. [Google Scholar] [CrossRef]
- Schomburg, L.; Schweizer, U. Hierarchical regulation of selenoprotein expression and sex-specific effects of selenium. Biochim. Biophys. Acta BBA Gen. Subj. 2009, 1790, 1453–1462. [Google Scholar] [CrossRef]
- Kipp, A.; Banning, A.; van Schothorst, E.M.; Méplan, C.; Schomburg, L.; Evelo, C.; Coort, S.; Gaj, S.; Keijer, J.; Hesketh, J.; et al. Four selenoproteins, protein biosynthesis, and Wnt signalling are particularly sensitive to limited selenium intake in mouse colon. Mol. Nutr. Food Res. 2009, 53, 1561–1572. [Google Scholar] [CrossRef]
- Sunde, R.A.; Raines, A.M. Selenium regulation of the selenoprotein and nonselenoprotein transcriptomes in rodents. Adv. Nutr. 2011, 2, 138–150. [Google Scholar] [CrossRef]
- Olson, G.E.; Winfrey, V.P.; NagDas, S.K.; Hill, K.E.; Burk, R.F. Apolipoprotein E receptor-2 (ApoER2) mediates selenium uptake from selenoprotein P by the mouse testis. J. Biol. Chem. 2007, 282, 12290–12297. [Google Scholar] [CrossRef]
- Pietschmann, N.; Rijntjes, E.; Hoeg, A.; Stoedter, M.; Schweizer, U.; Seemann, P.; Schomburg, L. Selenoprotein P is the essential selenium transporter for bones. Metallomics 2014, 6, 1043–1049. [Google Scholar] [CrossRef]
- Chiu-Ugalde, J.; Theilig, F.; Behrends, T.; Drebes, J.; Sieland, C.; Subbarayal, P.; Köhrle, J.; Hammes, A.; Schomburg, L.; Schweizer, U. Mutation of megalin leads to urinary loss of selenoprotein P and selenium deficiency in serum, liver, kidneys and brain. Biochem. J. 2010, 431, 103–111. [Google Scholar] [CrossRef] [PubMed]
- Olm, E.; Fernandes, A.P.; Hebert, C.; Rundlöf, A.-K.; Larsen, E.H.; Danielsson, O.; Björnstedt, M. Extracellular thiol-assisted selenium uptake dependent on the xc− cystine transporter explains the cancer-specific cytotoxicity of selenite. Proc. Natl. Acad. Sci. USA 2009, 106, 11400–11405. [Google Scholar] [CrossRef]
- Carlisle, A.E.; Lee, N.; Matthew-Onabanjo, A.N.; Spears, M.E.; Park, S.J.; Youkana, D.; Doshi, M.B.; Peppers, A.; Li, R.; Joseph, A.B. Selenium detoxification is required for cancer-cell survival. Nat. Metab. 2020, 2, 603–611. [Google Scholar] [CrossRef] [PubMed]
- Andreini, C.; Banci, L.; Bertini, I.; Rosato, A. Counting the zinc-proteins encoded in the human genome. J. Proteome Res. 2006, 5, 196–201. [Google Scholar] [CrossRef] [PubMed]
- Andreini, C.; Banci, L.; Bertini, I.; Rosato, A. Zinc through the three domains of life. J. Proteome Res. 2006, 5, 3173–3178. [Google Scholar] [CrossRef]
- McCall, K.A.; Huang, C.C.; Fierke, C.A. Function and mechanism of zinc metalloenzymes. J. Nutr. 2000, 130, 1437S–1446S. [Google Scholar] [CrossRef]
- Williams, R. The biochemistry of zinc. Polyhedron 1987, 6, 61–69. [Google Scholar] [CrossRef]
- Lichten, L.A.; Cousins, R.J. Mammalian zinc transporters: Nutritional and physiologic regulation. Annu. Rev. Nutr. 2009, 29, 153–176. [Google Scholar] [CrossRef]
- Kambe, T.; Tsuji, T.; Hashimoto, A.; Itsumura, N. The physiological, biochemical, and molecular roles of zinc transporters in zinc homeostasis and metabolism. Physiol. Rev. 2015, 95, 749–784. [Google Scholar] [CrossRef]
- Coyle, P.; Philcox, J.; Carey, L.; Rofe, A. Metallothionein: The multipurpose protein. Cell. Mol. Life Sci. CMLS 2002, 59, 627–647. [Google Scholar] [CrossRef]
- Zangger, K.; Öz, G.; Haslinger, E.; Kunert, O.; Armitage, I.M. Nitric oxide selectively releases metals from the N-terminal domain of metallothioneins: Potential role at inflammatory sites. FASEB J. 2001, 15, 1303–1305. [Google Scholar] [CrossRef] [PubMed]
- Radtke, F.; Heuchel, R.; Georgiev, O.; Hergersberg, M.; Gariglio, M.; Dembic, Z.; Schaffner, W. Cloned transcription factor MTF-1 activates the mouse metallothionein I promoter. EMBO J. 1993, 12, 1355–1362. [Google Scholar] [CrossRef] [PubMed]
- Chung, M.J.; Hogstrand, C.; Lee, S.-J. Cytotoxicity of nitric oxide is alleviated by zinc-mediated expression of antioxidant genes. Exp. Biol. Med. 2006, 231, 1555–1563. [Google Scholar] [CrossRef] [PubMed]
- Smirnova, I.V.; Bittel, D.C.; Ravindra, R.; Jiang, H.; Andrews, G.K. Zinc and cadmium can promote rapid nuclear translocation of metal response element-binding transcription factor-1. J. Biol. Chem. 2000, 275, 9377–9384. [Google Scholar] [CrossRef]
- Zhang, B.; Georgiev, O.; Hagmann, M.; Günes, C.; Cramer, M.; Faller, P.; Vasák, M.; Schaffner, W. Activity of metal-responsive transcription factor 1 by toxic heavy metals and H2O2 in vitro is modulated by metallothionein. Mol. Cell. Biol. 2003, 23, 8471–8485. [Google Scholar] [CrossRef]
- Andrews, G.K. Regulation of metallothionein gene expression by oxidative stress and metal ions. Biochem. Pharmacol. 2000, 59, 95–104. [Google Scholar] [CrossRef]
- Langmade, S.J.; Ravindra, R.; Daniels, P.J.; Andrews, G.K. The transcription factor MTF-1 mediates metal regulation of the mouse ZnT1 gene. J. Biol. Chem. 2000, 275, 34803–34809. [Google Scholar] [CrossRef]
- Guo, L.; Lichten, L.A.; Ryu, M.-S.; Liuzzi, J.P.; Wang, F.; Cousins, R.J. STAT5-glucocorticoid receptor interaction and MTF-1 regulate the expression of ZnT2 (Slc30a2) in pancreatic acinar cells. Proc. Natl. Acad. Sci. USA 2010, 107, 2818–2823. [Google Scholar] [CrossRef]
- Mehta, A.J.; Joshi, P.C.; Fan, X.; Brown, L.A.S.; Ritzenthaler, J.D.; Roman, J.; Guidot, D.M. Zinc supplementation restores PU. 1 and Nrf2 nuclear binding in alveolar macrophages and improves redox balance and bacterial clearance in the lungs of alcohol-fed rats. Alcohol. Clin. Exp. Res. 2011, 35, 1519–1528. [Google Scholar] [CrossRef]
- Gao, L.; Fan, Y.; Zhang, X.; Yang, L.; Huang, W.; Hang, T.; Li, M.; Du, S.; Ma, J. Zinc supplementation inhibits the high glucose-induced EMT of peritoneal mesothelial cells by activating the Nrf2 antioxidant pathway. Mol. Med. Rep. 2019, 20, 655–663. [Google Scholar] [CrossRef]
- Lu, X.; Zhang, Q.; Xu, L.; Lin, X.; Fu, J.; Wang, X.; Liu, Y.; Lin, Y.; Li, B.; Wang, R. Zinc is essential for the transcription function of the PGC-1α/Nrf2 signaling pathway in human primary endometrial stromal cells. Am. J. Physiol. Cell Physiol. 2020, 318, C640–C648. [Google Scholar] [CrossRef]
- Suzuki, T.; Takahashi, J.; Yamamoto, M. Molecular Basis of the KEAP1-NRF2 Signaling Pathway. Mol. Cells 2023, 46, 133–141. [Google Scholar] [CrossRef] [PubMed]
- Occhiuto, C.J.; Moerland, J.A.; Leal, A.S.; Gallo, K.A.; Liby, K.T. The Multi-Faceted Consequences of NRF2 Activation throughout Carcinogenesis. Mol. Cells 2023, 46, 176–186. [Google Scholar] [CrossRef] [PubMed]
- McMahon, M.; Lamont, D.J.; Beattie, K.A.; Hayes, J.D. Keap1 perceives stress via three sensors for the endogenous signaling molecules nitric oxide, zinc, and alkenals. Proc. Natl. Acad. Sci. USA 2010, 107, 18838–18843. [Google Scholar] [CrossRef]
- McMahon, M.; Swift, S.R.; Hayes, J.D. Zinc-binding triggers a conformational-switch in the cullin-3 substrate adaptor protein KEAP1 that controls transcription factor NRF2. Toxicol. Appl. Pharmacol. 2018, 360, 45–57. [Google Scholar] [CrossRef]
- Torrente, L.; DeNicola, G.M. Targeting NRF2 and its downstream processes: Opportunities and challenges. Annu. Rev. Pharmacol. Toxicol. 2022, 62, 279–300. [Google Scholar] [CrossRef]
- Banning, A.; Deubel, S.; Kluth, D.; Zhou, Z.; Brigelius-Flohé, R. The GI-GPx gene is a target for Nrf2. Mol. Cell. Biol. 2005, 25, 4914–4923. [Google Scholar] [CrossRef]
- Hintze, K.J.; Wald, K.A.; Zeng, H.; Jeffery, E.H.; Finley, J.W. Thioredoxin reductase in human hepatoma cells is transcriptionally regulated by sulforaphane and other electrophiles via an antioxidant response element. J. Nutr. 2003, 133, 2721–2727. [Google Scholar] [CrossRef]
- Gu, J.; Cheng, Y.; Wu, H.; Kong, L.; Wang, S.; Xu, Z.; Zhang, Z.; Tan, Y.; Keller, B.B.; Zhou, H.; et al. Metallothionein Is Downstream of Nrf2 and Partially Mediates Sulforaphane Prevention of Diabetic Cardiomyopathy. Diabetes 2017, 66, 529–542. [Google Scholar] [CrossRef]
- Banning, A.; Florian, S.; Deubel, S.; Thalmann, S.; Müller-Schmehl, K.; Jacobasch, G.; Brigelius-Flohé, R. GPx2 counteracts PGE2 production by dampening COX-2 and mPGES-1 expression in human colon cancer cells. Antioxid. Redox Signal. 2008, 10, 1491–1500. [Google Scholar] [CrossRef]
- Müller, M.; Banning, A.; Brigelius-Flohé, R.; Kipp, A. Nrf2 target genes are induced under marginal selenium-deficiency. Genes Nutr. 2010, 5, 297–307. [Google Scholar] [CrossRef] [PubMed]
- Krehl, S.; Loewinger, M.; Florian, S.; Kipp, A.P.; Banning, A.; Wessjohann, L.A.; Brauer, M.N.; Iori, R.; Esworthy, R.S.; Chu, F.-F.; et al. Glutathione peroxidase-2 and selenium decreased inflammation and tumors in a mouse model of inflammation-associated carcinogenesis whereas sulforaphane effects differed with selenium supply. Carcinogenesis 2012, 33, 620–628. [Google Scholar] [CrossRef] [PubMed]
- Florian, S.; Krehl, S.; Loewinger, M.; Kipp, A.; Banning, A.; Esworthy, S.; Chu, F.-F.; Brigelius-Flohé, R. Loss of GPx2 increases apoptosis, mitosis, and GPx1 expression in the intestine of mice. Free Radic. Biol. Med. 2010, 49, 1694–1702. [Google Scholar] [CrossRef]
- Böcher, M.; Böldicke, T.; Kieß, M.; Bilitewski, U. Synthesis of mono-and bifunctional peptide–dextran conjugates for the immobilization of peptide antigens on ELISA plates: Properties and application. J. Immunol. Methods 1997, 208, 191–202. [Google Scholar] [CrossRef] [PubMed]
- Schwarz, M.; Lossow, K.; Schirl, K.; Hackler, J.; Renko, K.; Kopp, J.F.; Schwerdtle, T.; Schomburg, L.; Kipp, A.P. Copper interferes with selenoprotein synthesis and activity. Redox Biol. 2020, 37, 101746. [Google Scholar] [CrossRef] [PubMed]
- Panda, H.; Wen, H.; Suzuki, M.; Yamamoto, M. Multifaceted Roles of the KEAP1–NRF2 System in Cancer and Inflammatory Disease Milieu. Antioxidants 2022, 11, 538. [Google Scholar] [CrossRef] [PubMed]
- Hübner, C.; Haase, H. Interactions of zinc-and redox-signaling pathways. Redox Biol. 2021, 41, 101916. [Google Scholar] [CrossRef]
- Dinkova-Kostova, A.T.; Holtzclaw, W.D.; Kensler, T.W. The role of Keap1 in cellular protective responses. Chem. Res. Toxicol. 2005, 18, 1779–1791. [Google Scholar] [CrossRef]
- Tainer, J.A.; Getzoff, E.D.; Beem, K.M.; Richardson, J.S.; Richardson, D.C. Determination and analysis of the 2 Å structure of copper, zinc superoxide dismutase. J. Mol. Biol. 1982, 160, 181–217. [Google Scholar] [CrossRef]
- Wolfram, T.; Schwarz, M.; Reuß, M.; Lossow, K.; Ost, M.; Klaus, S.; Schwerdtle, T.; Kipp, A.P. N-acetylcysteine as modulator of the essential trace elements copper and zinc. Antioxidants 2020, 9, 1117. [Google Scholar] [CrossRef]
- Park, S.-H.; Kim, J.-H.; Chi, G.Y.; Kim, G.-Y.; Chang, Y.-C.; Moon, S.-K.; Nam, S.-W.; Kim, W.-J.; Yoo, Y.H.; Choi, Y.H. Induction of apoptosis and autophagy by sodium selenite in A549 human lung carcinoma cells through generation of reactive oxygen species. Toxicol. Lett. 2012, 212, 252–261. [Google Scholar] [CrossRef] [PubMed]
- Burk, R.F.; Hill, K.E.; Nakayama, A.; Mostert, V.; Levander, X.A.; Motley, A.K.; Johnson, D.A.; Johnson, J.A.; Freeman, M.L.; Austin, L.M. Selenium deficiency activates mouse liver Nrf2–ARE but vitamin E deficiency does not. Free Radic. Biol. Med. 2008, 44, 1617–1623. [Google Scholar] [CrossRef] [PubMed]
- Sengupta, A.; Carlson, B.A.; Weaver, J.A.; Novoselov, S.V.; Fomenko, D.E.; Gladyshev, V.N.; Hatfield, D.L. A functional link between housekeeping selenoproteins and phase II enzymes. Biochem. J. 2008, 413, 151–161. [Google Scholar] [CrossRef]
- Suvorova, E.S.; Lucas, O.; Weisend, C.M.; Rollins, M.F.; Merrill, G.F.; Capecchi, M.R.; Schmidt, E.E. Cytoprotective Nrf2 pathway is induced in chronically txnrd 1-deficient hepatocytes. PLoS ONE 2009, 4, e6158. [Google Scholar] [CrossRef]
- Carlson, B.A.; Tobe, R.; Yefremova, E.; Tsuji, P.A.; Hoffmann, V.J.; Schweizer, U.; Gladyshev, V.N.; Hatfield, D.L.; Conrad, M. Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration. Redox Biol. 2016, 9, 22–31. [Google Scholar] [CrossRef]
- Tauber, S.; Sieckmann, M.K.; Erler, K.; Stahl, W.; Klotz, L.-O.; Steinbrenner, H. Activation of Nrf2 by electrophiles is largely independent of the selenium status of HepG2 cells. Antioxidants 2021, 10, 167. [Google Scholar] [CrossRef]
- Cebula, M.; Schmidt, E.E.; Arnér, E.S. TrxR1 as a potent regulator of the Nrf2-Keap1 response system. Antioxid. Redox Signal. 2015, 23, 823–853. [Google Scholar] [CrossRef]
- Zhong, C.-C.; Zhao, T.; Hogstrand, C.; Song, C.-C.; Zito, E.; Tan, X.-Y.; Xu, Y.-C.; Song, Y.-F.; Wei, X.-L.; Luo, Z. Copper induces liver lipotoxicity disease by up-regulating Nrf2 expression via the activation of MTF-1 and inhibition of SP1/Fyn pathway. Biochim. Biophys. Acta BBA Mol. Basis Dis. 2023, 1869, 166752. [Google Scholar] [CrossRef]
- McDermott, J.R.; Geng, X.; Jiang, L.; Gálvez-Peralta, M.; Chen, F.; Nebert, D.W.; Liu, Z. Zinc-and bicarbonate-dependent ZIP8 transporter mediates selenite uptake. Oncotarget 2016, 7, 35327. [Google Scholar] [CrossRef]
- Liu, L.; Geng, X.; Cai, Y.; Copple, B.; Yoshinaga, M.; Shen, J.; Nebert, D.W.; Wang, H.; Liu, Z. Hepatic ZIP8 deficiency is associated with disrupted selenium homeostasis, liver pathology, and tumor formation. Am. J. Physiol. Gastrointest. Liver Physiol. 2018, 315, G569–G579. [Google Scholar] [CrossRef]
- Fan, Z.; Wirth, A.; Chen, D.; Wruck, C.; Rauh, M.; Buchfelder, M.; Savaskan, N. Nrf2-Keap1 pathway promotes cell proliferation and diminishes ferroptosis. Oncogenesis 2017, 6, e371. [Google Scholar] [CrossRef] [PubMed]
- Tsujita, T.; Peirce, V.; Baird, L.; Matsuyama, Y.; Takaku, M.; Walsh, S.V.; Griffin, J.L.; Uruno, A.; Yamamoto, M.; Hayes, J.D. Transcription factor Nrf1 negatively regulates the cystine/glutamate transporter and lipid-metabolizing enzymes. Mol. Cell. Biol. 2014, 34, 3800–3816. [Google Scholar] [CrossRef] [PubMed]
- Fantone, S.; Piani, F.; Olivieri, F.; Rippo, M.R.; Sirico, A.; Di Simone, N.; Marzioni, D.; Tossetta, G. Role of SLC7A11/xCT in Ovarian Cancer. Int. J. Mol. Sci. 2024, 25, 587. [Google Scholar] [CrossRef] [PubMed]
Antibody | Company | Dilution in T-TBS |
---|---|---|
rabbit anti-APOER2 | Abcam (108208) | 1:500 in 5% non-fat dry milk |
rabbit anti-GPX1 | Abcam (8850) | 1:5000 |
rabbit anti-GPX2 | [45] | 1:1000 |
rabbit anti-GPX4 | Abcam (125066) | 1:5000 |
rabbit anti-MT | Abcam (192385) | 1:1000 |
rabbit anti-MTF-1 | Novus Biologicals (86380) | 1:250 |
rabbit anti-NQO1 | Abcam (34173) | 1:4000 |
rabbit anti-NRF2 | Cell Signaling (12721) | 1:1000 |
rabbit anti-SELENOH | Abcam (151023) | 1:500 |
rabbit anti-TXNRD1 | Abcam (16840) | 1:5000 |
rabbit anti-TXNRD2 | Abcam (180493) | 1:1000 |
rabbit anti-XCT | Cell Signaling (12691) | 1:1000 in 5% BSA |
Primer | RefSeq-ID | Sequence (5′ → 3′) |
---|---|---|
GAPDH | NM_001289746.1 | ACTCATGACCACAGTCCATGCC GATGACCTTGCCCACAGCCT |
GCLC | NM_001498.3 | TGCTGTCTCCAGGTGACATTCCA GGAGATGCAGCACTCAAAGCCA |
GCLM | NM_002061.3 | GTTGACATGGCCTGTTCAGTCCT CCCAGTAAGGCTGTAAATGCTCCA |
GPX1 | NM_000581.2 | TACTTATCGAGAATGTGGCGTCCC TTGGCGTTCTCCTGATGCCC |
GPX2 | NM_002083.4 | GTGCTGATTGAGAATGTGGC AGGATGCTCGTTCTGCCCA |
HMOX1 | NM_002133.2 | CAACAAAGTGCAAGATTCTGCCC CTACAGCAACTGTCGCCACC |
HPRT | NM_000194.2 | TGGCGTCGTGATTAGTGATG GGCCTCCCATCTCCTTCAT |
MT2A | NM_005953.3 | AGGGCTGCATCTGCAAAGGG TAGCAAACGGTCACGGTCAGGG |
NQO1 | NM_001025434.1 | CATCACAGGTAAACTGAAGGACCC CTCTGGAATATCACAAGGTCTGCG |
RPL13A | NM_012423.2 | AGCCTACAAGAAAGTTTGCCTATCTG TAGTGGATCTTGGCTTTCTCTTTCCT |
SELENOH | NM_170746.2 | GCTTCCAGTAAAGGTGAACCCGA TCAGGGAATTTGAGTTTGCGTGG |
SRXN1 | NM_080725.1 | CTCAGTGCTCGTTACTTCATGGTC GTTTGGCCCTTCCTCTTCCTCC |
TXNRD1 | NM_015762.1 | GTGTTGTGGGCTTTCACGTACTG TGTTGTGAATACCTCTGCACAGAC |
TXNRD2 | NM_006440.3 | GTTCCCACGACCGTCTTCAC GTGATAGACCTCAACATGCTCCTG |
ZIP1 | NM_001271958.2 | ATGAAGGCTCAGCTTCCCGC AGCCAGGTAGTCAGGCAGCA |
ZIP8 | NM_001135146.2 | ATGGTCAGAATGGTCATACCCAC GCAGGATTTGCATAGCATGTCAC |
ZIP14 | NM_001128431.2 | GGACCTGGACCACATGATTCCT GTAGCGGACACCTTTCAGCCA |
ZNT1 | NM_021194.3 | GACCAGGAGGAGACCAACAC TCACCACTTCTGGGGTTTTC |
ZNT2 | NM_001004434.3 | CCAGAGCAACCATCACTGCCA GGTACCCACCAACGACTTCTCC |
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Löser, A.; Schwarz, M.; Kipp, A.P. NRF2 and Thioredoxin Reductase 1 as Modulators of Interactions between Zinc and Selenium. Antioxidants 2024, 13, 1211. https://doi.org/10.3390/antiox13101211
Löser A, Schwarz M, Kipp AP. NRF2 and Thioredoxin Reductase 1 as Modulators of Interactions between Zinc and Selenium. Antioxidants. 2024; 13(10):1211. https://doi.org/10.3390/antiox13101211
Chicago/Turabian StyleLöser, Alina, Maria Schwarz, and Anna Patricia Kipp. 2024. "NRF2 and Thioredoxin Reductase 1 as Modulators of Interactions between Zinc and Selenium" Antioxidants 13, no. 10: 1211. https://doi.org/10.3390/antiox13101211
APA StyleLöser, A., Schwarz, M., & Kipp, A. P. (2024). NRF2 and Thioredoxin Reductase 1 as Modulators of Interactions between Zinc and Selenium. Antioxidants, 13(10), 1211. https://doi.org/10.3390/antiox13101211