Regeneration of glutathione by α-lipoic acid via Nrf2/ARE signaling pathway alleviates cadmium-induced HepG2 cell toxicity

Environmental Toxicology and Pharmacology

Volumn 51, Issue , 2017, Pages 30-37

  Zhang, Jiayu ^a   Zhou, Xue ^a   Wu, Wenbo ^a   Wang, Jiachun ^a   Xie, Hong ^a   Wu, Zhigang ^a  

^a HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

Author keywords

Cadmium; Glutathione; Nrf2; Regeneration; Lipoic acid

Indexed keywords

BRUSATOL; CADMIUM; GLUTAMATE CYSTEINE LIGASE; GLUTATHIONE; MESSENGER RNA; THIOCTIC ACID; TRANSCRIPTION FACTOR NRF2; ANTIOXIDANT; GLUTATHIONE REDUCTASE; NFE2L2 PROTEIN, HUMAN; POLLUTANT;

ANTIOXIDANT RESPONSIVE ELEMENT; ARTICLE; CELL STIMULATION; CONTROLLED STUDY; CYTOTOXICITY; ENZYME REACTIVATION; ENZYME REPRESSION; HEP-G2 CELL LINE; HORMONE DETERMINATION; HORMONE SYNTHESIS; HUMAN; HUMAN CELL; PROTEIN DEPLETION; PROTEIN EXPRESSION; PROTEIN SYNTHESIS; RECEPTOR BLOCKING; SIGNAL TRANSDUCTION; CELL CULTURE TECHNIQUE; CELL SURVIVAL; DRUG EFFECTS; GENETICS; METABOLISM; OXIDATIVE STRESS; PHYSIOLOGY; POLLUTANT; TOXICITY;

ANTIOXIDANT RESPONSE ELEMENTS; ANTIOXIDANTS; CADMIUM; CELL CULTURE TECHNIQUES; CELL SURVIVAL; ENVIRONMENTAL POLLUTANTS; GLUTAMATE-CYSTEINE LIGASE; GLUTATHIONE; GLUTATHIONE REDUCTASE; HEP G2 CELLS; HUMANS; NF-E2-RELATED FACTOR 2; OXIDATIVE STRESS; SIGNAL TRANSDUCTION; THIOCTIC ACID;

EID: 85014376398     PISSN: 13826689     EISSN: 18727077     Source Type: Journal    
DOI: 10.1016/j.etap.2017.02.022     Document Type: Article

References (59)

1. Ahmad, P., Sarwat, M., Bhat, N.A., Wani, M.R., Kazi, A.G., Tran, L.S., Alleviation of cadmium toxicity in Brassica juncea L. (Czern. & Coss.) by calcium application involves various physiological and biochemical strategies. PLoS One, 10(1), 2015, e0114571.
2. Ballatori, N., Krance, S.M., Notenboom, S., Shi, S., Tieu, K., Hammond, C.L., Glutathione dysregulation and the etiology and progression of human diseases. Biol. Chem. 390:3 (2009), 191–214.
3. Biswas, C., Shah, N., Muthu, M., La, P., Fernando, A.P., Sengupta, S., Yang, G., Dennery, P.A., Nuclear heme oxygenase-1 (HO-1) modulates subcellular distribution and activation of Nrf2, impacting metabolic and anti-oxidant defenses. J. Biol. Chem. 289:39 (2014), 26882–26894.
4. Chen, B., Lu, Y., Chen, Y., Cheng, J., The role of Nrf2 in oxidative stress-induced endothelial injuries. J. Endocrinol. 225:3 (2015), R83–99.
5. Cho, H.Y., Reddy, S.P., Kleeberger, S.R., Nrf2 defends the lung from oxidative stress. Antioxid. Redox Signal. 8:1–2 (2006), 76–87.
6. Deng, C., Sun, Z., Tong, G., Yi, W., Ma, L., Zhao, B., Cheng, L., Zhang, J., Cao, F., Yi, D., Alpha-lipoic acid reduces infarct size and preserves cardiac function in rat myocardial ischemia/reperfusion injury through activation of PI3K/Akt/Nrf2 pathway. PLoS One, 8(3), 2013, e58371.
7. Elshazly, S.M., El-Moselhy, M.A., Barakat, W., Insights in the mechanism underlying the protective effect of alpha-lipoic acid against acetaminophen-hepatotoxicity. Eur. J. Pharmacol. 726 (2014), 116–123.
8. Fei, M., Xie, Q., Zou, Y., He, R., Zhang, Y., Wang, J., Bo, L., Li, J., Deng, X., Alpha-lipoic acid protects mice against concanavalin A-induced hepatitis by modulating cytokine secretion and reducing reactive oxygen species generation. Int. Immunopharmacol. 35 (2016), 53–60.
9. Fujita, H., Shiosaka, M., Ogino, T., Okimura, Y., Utsumi, T., Sato, E.F., Akagi, R., Inoue, M., Utsumi, K., Sasaki, J., Alpha-lipoic acid suppresses 6-hydroxydopamine-induced ROS generation and apoptosis through the stimulation of glutathione synthesis but not by the expression of heme oxygenase-1. Brain Res. 1206 (2008), 1–12.
10. Golbidi, S., Badran, M., Laher, I., Diabetes and alpha lipoic acid. Front. Pharmacol., 2, 2011, 69.
11. Goldring, C.E., Kitteringham, N.R., Elsby, R., Randle, L.E., Clement, Y.N., Williams, D.P., McMahon, M., Hayes, J.D., Itoh, K., Yamamoto, M., et al. Activation of hepatic Nrf2 in vivo by acetaminophen in CD-1 mice. Hepatology 39:5 (2004), 1267–1276.
12. Gomes, M.B., Negrato, C.A., Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use in diabetes and other chronic diseases. Diabetol. Metab. Syndr., 6(1), 2014, 80.
13. Goraca, A., Piechota, A., Huk-Kolega, H., Effect of alpha-lipoic acid on LPS-induced oxidative stress in the heart. J. Physiol. Pharmacol. 60:1 (2009), 61–68.
14. Gum, S.I., Cho, M.K., The amelioration of N-acetyl-p-benzoquinone imine toxicity by ginsenoside Rg3: the role of Nrf2-mediated detoxification and Mrp1/Mrp3 transports. Oxid. Med. Cell. Longev., 2013, 2013, 957947.
15. Harvey, C.J., Thimmulappa, R.K., Singh, A., Blake, D.J., Ling, G., Wakabayashi, N., Fujii, J., Myers, A., Biswal, S., Nrf2-regulated glutathione recycling independent of biosynthesis is critical for cell survival during oxidative stress. Free Radic. Biol. Med. 46:4 (2009), 443–453.
16. Huerta-Olvera, S.G., Macias-Barragan, J., Ramos-Marquez, M.E., Armendariz-Borunda, J., Diaz-Barriga, F., Siller-Lopez, F., Alpha-lipoic acid regulates heme oxygenase gene expression and nuclear Nrf2 activation as a mechanism of protection against arsenic exposure in HepG2 cells. Environ. Toxicol. Pharmacol. 29:2 (2010), 144–149.
17. Huerta-Olvera, S.G., Macias-Barragan, J., Ramos-Marquez, M.E., Armendariz-Borunda, J., Diaz-Barriga, F., Siller-Lopez, F., Alpha-lipoic acid regulates heme oxygenase gene expression and nuclear Nrf2 activation as a mechanism of protection against arsenic exposure in HepG2 cells. Environ. Toxicol. Pharmacol. 29:2 (2010), 144–149.
18. Huff, J., Lunn, R.M., Waalkes, M.P., Tomatis, L., Infante, P.F., Cadmium-induced cancers in animals and in humans. Int. J. Occup. Environ. Health 13:2 (2007), 202–212.
19. Ide, T., Effect of dietary alpha-lipoic acid on the mRNA expression of genes involved in drug metabolism and antioxidation system in rat liver. Br. J. Nutr. 112:3 (2014), 295–308.
20. Im, J.Y., Paik, S.G., Han, P.L., Cadmium-induced astroglial death proceeds via glutathione depletion. J. Neurosci. Res. 83:2 (2006), 301–308.
21. Kalinina, E.V., Chernov, N.N., Novichkova, M.D., Role of glutathione, glutathione transferase, and glutaredoxin in regulation of redox-dependent processes. Biochemistry (Mosc.) 79:13 (2014), 1562–1583.
22. Kaspar, J.W., Jaiswal, A.K., Tyrosine phosphorylation controls nuclear export of Fyn, allowing Nrf2 activation of cytoprotective gene expression. FASEB J. 25:3 (2011), 1076–1087.
23. Kaspar, J.W., Niture, S.K., Jaiswal, A.K., Antioxidant-induced INrf2 (Keap1) tyrosine 85 phosphorylation controls the nuclear export and degradation of the INrf2-Cul3-Rbx1 complex to allow normal Nrf2 activation and repression. J. Cell Sci. 125:Pt. 4 (2012), 1027–1038.
24. Kensler, T.W., Wakabayashi, N., Biswal, S., Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu. Rev. Pharmacol. Toxicol. 47 (2007), 89–116.
25. Kobayashi, A., Kang, M.I., Watai, Y., Tong, K.I., Shibata, T., Uchida, K., Yamamoto, M., Oxidative and electrophilic stresses activate Nrf2 through inhibition of ubiquitination activity of Keap1. Mol. Cell. Biol. 26:1 (2006), 221–229.
26. Krumschnabel, G., Ebner, H.L., Hess, M.W., Villunger, A., Apoptosis and necroptosis are induced in rainbow trout cell lines exposed to cadmium. Aquat. Toxicol. 99:1 (2010), 73–85.
27. Kukongviriyapan, U., Apaijit, K., Kukongviriyapan, V., Oxidative stress and cardiovascular dysfunction associated with cadmium exposure: beneficial effects of curcumin and tetrahydrocurcumin. Tohoku J. Exp. Med. 239:1 (2016), 25–38.
28. Lau, A., Whitman, S.A., Jaramillo, M.C., Zhang, D.D., Arsenic-mediated activation of the Nrf2-Keap1 antioxidant pathway. J. Biochem. Mol. Toxicol. 27:2 (2013), 99–105.
29. Lawal, A.O., Ellis, E., Differential sensitivity and responsiveness of three human cell lines HepG2, 1321N1 and HEK 293 to cadmium. J. Toxicol. Sci. 35:4 (2010), 465–478.
30. Lu, M.C., Ji, J.A., Jiang, Z.Y., You, Q.D., The Keap1-Nrf2-ARE pathway as a potential preventive and therapeutic target: an update. Med. Res. Rev. 36:5 (2016), 924–963.
31. Moodley, S., Koorbanally, N.A., Moodley, T., Ramjugernath, D., Pillay, M., The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay is a rapid, cheap, screening test for the in vitro anti-tuberculous activity of chalcones. J. Microbiol. Methods 104 (2014), 72–78.
32. Moraes, T.B., Zanin, F., Da, R.A., de Oliveira, A., Coelho, J., Petrillo, F., Wajner, M., Dutra-Filho, C.S., Lipoic acid prevents oxidative stress in vitro and in vivo by an acute hyperphenylalaninemia chemically-induced in rat brain. J. Neurol. Sci. 292:1–2 (2010), 89–95.
33. Niture, S.K., Jain, A.K., Jaiswal, A.K., Antioxidant-induced modification of INrf2 cysteine 151 and PKC-delta-mediated phosphorylation of Nrf2 serine 40 are both required for stabilization and nuclear translocation of Nrf2 and increased drug resistance. J. Cell Sci. 122:Pt. 24 (2009), 4452–4464.
34. Reddy, N.M., Kleeberger, S.R., Cho, H.Y., Yamamoto, M., Kensler, T.W., Biswal, S., Reddy, S.P., Deficiency in Nrf2-GSH signaling impairs type II cell growth and enhances sensitivity to oxidants. Am. J. Respir. Cell Mol. Biol. 37:1 (2007), 3–8.
35. Ren, D., Villeneuve, N.F., Jiang, T., Wu, T., Lau, A., Toppin, H.A., Zhang, D.D., Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism. Proc. Natl. Acad. Sci. U. S. A. 108:4 (2011), 1433–1438.
36. Rochette, L., Ghibu, S., Muresan, A., Vergely, C., Alpha-lipoic acid: molecular mechanisms and therapeutic potential in diabetes. Can. J. Physiol. Pharmacol. 93:12 (2015), 1021–1027.
37. Saing, T., Lagman, M., Castrillon, J., Gutierrez, E., Guilford, F.T., Venketaraman, V., Analysis of glutathione levels in the brain tissue samples from HIV-1-positive individuals and subject with Alzheimer's disease and its implication in the pathophysiology of the disease process. BBA Clin. 6 (2016), 38–44.
38. Sanders, A.P., Smeester, L., Rojas, D., DeBussycher, T., Wu, M.C., Wright, F.A., Zhou, Y.H., Laine, J.E., Rager, J.E., Swamy, G.K., et al. Cadmium exposure and the epigenome: exposure-associated patterns of DNA methylation in leukocytes from mother-baby pairs. Epigenetics 9:2 (2014), 212–221.
39. Shi, H., Ye, T., Han, N., Bian, H., Liu, X., Chan, Z., Hydrogen sulfide regulates abiotic stress tolerance and biotic stress resistance in Arabidopsis. J. Integr. Plant Biol. 57:7 (2015), 628–640.
40. Shi, C., Zhou, X., Zhang, J., Wang, J., Xie, H., Wu, Z., Alpha-lipoic acid protects against the cytotoxicity and oxidative stress induced by cadmium in HepG2 cells through regeneration of glutathione by glutathione reductase via Nrf2/ARE signaling pathway. Environ. Toxicol. Pharmacol. 45 (2016), 274–281.
41. Son, Y.O., Wang, L., Poyil, P., Budhraja, A., Hitron, J.A., Zhang, Z., Lee, J.C., Shi, X., Cadmium induces carcinogenesis in BEAS-2B cells through ROS-dependent activation of PI3K/AKT/GSK-3beta/beta-catenin signaling. Toxicol. Appl. Pharmacol. 264:2 (2012), 153–160.
42. Steele, M.L., Fuller, S., Patel, M., Kersaitis, C., Ooi, L., Munch, G., Effect of Nrf2 activators on release of glutathione, cysteinylglycine and homocysteine by human U373 astroglial cells. Redox Biol. 1 (2013), 441–445.
43. Sueblinvong, V., Tseng, V., Smith, T., Saghafi, R., Mills, S.T., Neujahr, D.C., Guidot, D.M., TGFbeta1 mediates alcohol-induced Nrf2 suppression in lung fibroblasts. Alcohol. Clin. Exp. Res. 38:11 (2014), 2731–2742.
44. Suh, J.H., Shenvi, S.V., Dixon, B.M., Liu, H., Jaiswal, A.K., Liu, R.M., Hagen, T.M., Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. Proc. Natl. Acad. Sci. U. S. A. 101:10 (2004), 3381–3386.
45. Tabassum, H., Parvez, S., Pasha, S.T., Banerjee, B.D., Raisuddin, S., Protective effect of lipoic acid against methotrexate-induced oxidative stress in liver mitochondria. Food Chem. Toxicol. 48:7 (2010), 1973–1979.
46. Valdecantos, M.P., Prieto-Hontoria, P.L., Pardo, V., Modol, T., Santamaria, B., Weber, M., Herrero, L., Serra, D., Muntane, J., Cuadrado, A., et al. Essential role of Nrf2 in the protective effect of lipoic acid against lipoapoptosis in hepatocytes. Free Radic. Biol. Med. 84 (2015), 263–278.
47. Vari, R., D'Archivio, M., Filesi, C., Carotenuto, S., Scazzocchio, B., Santangelo, C., Giovannini, C., Masella, R., Protocatechuic acid induces antioxidant/detoxifying enzyme expression through JNK-mediated Nrf2 activation in murine macrophages. J. Nutr. Biochem. 22:5 (2011), 409–417.
48. Voloboueva, L.A., Liu, J., Suh, J.H., Ames, B.N., Miller, S.S., (R)-Alpha-lipoic acid protects retinal pigment epithelial cells from oxidative damage. Invest. Ophthalmol. Vis. Sci. 46:11 (2005), 4302–4310.
49. Wagner, A.E., Ernst, I.M., Birringer, M., Sancak, O., Barella, L., Rimbach, G., A combination of lipoic acid plus coenzyme Q10 induces PGC1alpha, a master switch of energy metabolism, improves stress response, and increases cellular glutathione levels in cultured C2C12 skeletal muscle cells. Oxid. Med. Cell. Longev., 2012, 2012, 835970.
50. Xie, J.M., Li, B., Yu, H.P., Gao, Q.G., Li, W., Wu, H.R., Qin, Z.H., TIGAR has a dual role in cancer cell survival through regulating apoptosis and autophagy. Cancer Res. 74:18 (2014), 5127–5138.
51. Xu, Y., Zhou, X., Shi, C., Wang, J., Wu, Z., Alpha-lipoic acid protects against the oxidative stress and cytotoxicity induced by cadmium in HepG2 cells through regenerating glutathione regulated by glutamate-cysteine ligase. Toxicol. Mech. Methods 25:8 (2015), 596–603.
52. Yang, H., Magilnick, N., Ou, X., Lu, S.C., Tumour necrosis factor alpha induces co-ordinated activation of rat GSH synthetic enzymes via nuclear factor kappaB and activator protein-1. Biochem. J. 391:Pt. 2 (2005), 399–408.
53. Yang, Y.C., Lii, C.K., Lin, A.H., Yeh, Y.W., Yao, H.T., Li, C.C., Liu, K.L., Chen, H.W., Induction of glutathione synthesis and heme oxygenase 1 by the flavonoids butein and phloretin is mediated through the ERK/Nrf2 pathway and protects against oxidative stress. Free Radic. Biol. Med. 51:11 (2011), 2073–2081.
54. Yao, J.K., Leonard, S., Reddy, R., Altered glutathione redox state in schizophrenia. Dis. Mark. 22:1–2 (2006), 83–93.
55. Zhang, P., Xu, Y., Li, L., Jiang, Q., Wang, M., Jin, L., In vitro protective effects of pyrroloquinoline quinone on methylmercury-induced neurotoxicity. Environ. Toxicol. Pharmacol. 27:1 (2009), 103–110.
56. Zheng, L., Meng, Y., Ma, J., Zhao, X., Cheng, T., Ji, J., Chang, E., Meng, C., Deng, N., Chen, L., et al. Transcriptomic analysis reveals importance of ROS and phytohormones in response to short-term salinity stress in Populus tomentosa. Front. Plant Sci., 6, 2015, 678.
57. Zhou, Y.J., Zhang, S.P., Liu, C.W., Cai, Y.Q., The protection of selenium on ROS mediated-apoptosis by mitochondria dysfunction in cadmium-induced LLC-PK(1) cells. Toxicol. In Vitro 23:2 (2009), 288–294.
58. Zou, X., Feng, Z., Li, Y., Wang, Y., Wertz, K., Weber, P., Fu, Y., Liu, J., Stimulation of GSH synthesis to prevent oxidative stress-induced apoptosis by hydroxytyrosol in human retinal pigment epithelial cells: activation of Nrf2 and JNK-p62/SQSTM1 pathways. J. Nutr. Biochem. 23:8 (2012), 994–1006.
59. Zou, H., Liu, X., Han, T., Hu, D., Yuan, Y., Gu, J., Bian, J., Liu, Z., Alpha-lipoic acid protects against cadmium-induced hepatotoxicity via calcium signalling and gap junctional intercellular communication in rat hepatocytes. J. Toxicol. Sci. 40:4 (2015), 469–477.