Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
권호 표지
DOI QR코드

DOI QR Code

Adaptive Responses to Electrophilic Stress and Reactive Sulfur Species as their Regulator Molecules

  • Kumagai, Yoshito (Environmental Biology Laboratory, Faculty of Medicine, University of Tsukuba) ;
  • Akiyama, Masahiro (Environmental Biology Laboratory, Faculty of Medicine, University of Tsukuba) ;
  • Unoki, Takamitsu (Department of Basic Medical Sciences, National Institute for Minamata Disease)
  • Received : 2019.07.10
  • Accepted : 2019.08.26
  • Published : 2019.10.15
Download PDF
⟨ Previous Next ⟩

Abstract

We are exposed to numerous xenobiotic electrophiles on a daily basis through the environment, lifestyle, and dietary habits. Although such reactive species have been associated with detrimental effects, recent accumulated evidence indicates that xenobiotic electrophiles appear to act as signaling molecules. In this review, we introduce our findings on 1) activation of various redox signaling pathways involved in cell proliferation, detoxification/excretion of electrophiles, quality control of cellular proteins, and cell survival during exposure to xenobiotic electrophiles at low concentrations through covalent modification of thiol groups in sensor proteins, and 2) negative regulation of reactive sulfur species (RSS) in the modulation of redox signaling and toxicity caused by xenobiotic electrophiles.

Keywords

References

  1. Eiguren-Fernandez, A., Miguel, A.H., Di Stefano, E., Schmitz, D.A., Cho, A.K., Thurairatnam, S., Avol, E.L. and Froines, J.R. (2008) Atmospheric distribution of gas- and particlephase quinones in Southern California. Aerosol Sci. Tech., 42, 854-861. https://doi.org/10.1080/02786820802339546
  2. Chung, M.Y., Lazaro, R.A., Lim, D., Jackson, J., Lyon, J., Rendulic, D. and Hasson, A.S. (2006) Aerosol-borne quinones and reactive oxygen species generation by particulate matter extracts. Environ. Sci. Technol., 40, 4880-4886. https://doi.org/10.1021/es0515957
  3. Jakober, C.A., Riddle, S.G., Robert, M.A., Destaillats, H., Charles, M.J., Green, P.G. and Kleeman, M.J. (2007) Quinone emissions from gasoline and diesel motor vehicles. Environ. Sci. Technol., 41, 4548-4554. https://doi.org/10.1021/es062967u
  4. Shinyashiki, M., Eiguren-Fernandez, A., Schmitz, D.A., Di Stefano, E., Li, N., Linak, W.P., Cho, S.H., Froines, J.R. and Cho, A.K. (2009) Electrophilic and redox properties of diesel exhaust particles. Environ. Res., 109, 239-244. https://doi.org/10.1016/j.envres.2008.12.008
  5. Talhout, R., Schulz, T., Florek, E., van Benthem, J., Wester, P. and Opperhuizen, A. (2011) Hazardous compounds in tobacco smoke. Int. J. Environ. Res. Public Health, 8, 613-628. https://doi.org/10.3390/ijerph8020613
  6. Reznick, A.Z., Cross, C.E., Hu, M.L., Suzuki, Y.J., Khwaja, S., Safadi, A., Motchnik, P.A., Packer, L. and Halliwell, B. (1992) Modification of plasma proteins by cigarette smoke as measured by protein carbonyl formation. Biochem. J., 286, 607-611. https://doi.org/10.1042/bj2860607
  7. Potter, T.L. and Fagerson, I.S. (1990) Composition of coriander leaf volatiles. J. Agr. Food Chem., 38, 2054-2056. https://doi.org/10.1021/jf00101a011
  8. Wenzl, T., De La Calle, M.B. and Anklam, E. (2003) Analytical methods for the determination of acrylamide in food products: A review. Food Addit. Contam., 20, 885-902. https://doi.org/10.1080/02652030310001605051
  9. Koeman, J.H., van de Ven, W.S., de Goeij, J.J., Tjioe, P.S. and van Haaften, J.L. (1975) Mercury and selenium in marine mammals and birds. Sci. Total Environ., 3, 279-287. https://doi.org/10.1016/0048-9697(75)90052-2
  10. Peterson, C.L., Klawe, W.L. and Sharp, G.D. (1973) Mercury in Tunas - Review. Fish. Bull. (Wash. D. C.), 71, 603-613.
  11. Iwao, S., Sugita, M. and Tsuchiya, K. (1981) Some metabolic interrelationships among cadmium, lead, copper and zinc: results from a field survey in Cd-polluted areas in Japan. Part one: dietary intake of the heavy metals. Keio J. Med., 30, 17-36. https://doi.org/10.2302/kjm.30.17
  12. Bingham, F.T. (1979) Bioavailability of Cd to Food crops in relation to heavy metal content of sludge-amended soil. Environ. Health Perspect., 28, 39-43. https://doi.org/10.1289/ehp.792839
  13. Fujiki, H. (2014) Gist of Dr. Katsusaburo Yamagiwa's papers entitled "Experimental study on the pathogenesis of epithelial tumors" (I to VI reports). Cancer Sci., 105, 143-149. https://doi.org/10.1111/cas.12333
  14. Borgen, A., Darvey, H., Castagnoli, N., Crocker, T.T., Rasmussen, R.E. and Wang, I.Y. (1973) Metabolic conversion of benzo(a)pyrene by Syrian hamster liver microsomes and binding of metabolites to deoxyribonucleic acid. J. Med. Chem., 16, 502-506. https://doi.org/10.1021/jm00263a020
  15. Herenblum, I. (1945) 3:4-Benzpyrene from coal tar. Nature, 156, 601. https://doi.org/10.1038/156601a0
  16. Costa, E., Karczmar, A.G. and Vesell, E.S. (1989) Bernard B. Brodie and the rise of chemical pharmacology. Annu. Rev. Pharmacol. Toxicol., 29, 1-21. https://doi.org/10.1146/annurev.pa.29.040189.000245
  17. Brodie, B.B., Reid, W.D., Cho, A.K., Sipes, G., Krishna, G. and Gillette, J.R. (1971) Possible mechanism of liver necrosis caused by aromatic organic compounds. Proc. Natl. Acad. Sci. U.S.A., 68, 160-164. https://doi.org/10.1073/pnas.68.1.160
  18. Mitchell, J.R., Jollow, D.J., Potter, W.Z., Gillette, J.R. and Brodie, B.B. (1973) Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione. J. Pharmacol. Exp. Ther., 187, 211-217.
  19. Friling, R.S., Bensimon, A., Tichauer, Y. and Daniel, V. (1990) Xenobiotic-inducible expression of murine glutathione S-transferase Ya subunit gene is controlled by an electrophile-responsive element. Proc. Natl. Acad. Sci. U.S.A., 87, 6258-6262. https://doi.org/10.1073/pnas.87.16.6258
  20. Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J.D. and Yamamoto, M. (1999) Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev., 13, 76-86. https://doi.org/10.1101/gad.13.1.76
  21. Itoh, K., Chiba, T., Takahashi, S., Ishii, T., Igarashi, K., Katoh, Y., Oyake, T., Hayashi, N., Satoh, K., Hatayama, I., Yamamoto, M. and Nabeshima, Y. (1997) An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem. Biophys. Res. Commun., 236, 313-322. https://doi.org/10.1006/bbrc.1997.6943
  22. Esterbauer, H., Schaur, R.J. and Zollner, H. (1991) Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic. Biol. Med., 11, 81-128. https://doi.org/10.1016/0891-5849(91)90192-6
  23. Schopfer, F.J., Cipollina, C. and Freeman, B.A. (2011) Formation and signaling actions of electrophilic lipids. Chem. Rev., 111, 5997-6021. https://doi.org/10.1021/cr200131e
  24. Sawa, T., Zaki, M.H., Okamoto, T., Akuta, T., Tokutomi, Y., Kim-Mitsuyama, S., Ihara, H., Kobayashi, A., Yamamoto, M., Fujii, S., Arimoto, H. and Akaike, T. (2007) Protein S-guanylation by the biological signal 8-nitroguanosine 3',5'-cyclic monophosphate. Nat. Chem. Biol., 3, 727-735. https://doi.org/10.1038/nchembio.2007.33
  25. Suzuki, T. and Yamamoto, M. (2017) Stress-sensing mechanisms and the physiological roles of the Keap1-Nrf2 system during cellular stress. J. Biol. Chem., 292, 16817-16824. https://doi.org/10.1074/jbc.R117.800169
  26. Ahmed, K.A., Sawa, T. and Akaike, T. (2011) Protein cysteine S-guanylation and electrophilic signal transduction by endogenous nitro-nucleotides. Amino Acids, 41, 123-130. https://doi.org/10.1007/s00726-010-0535-1
  27. Kobayashi, E., Suzuki, T. and Yamamoto, M. (2013) Roles nrf2 plays in myeloid cells and related disorders. Oxid. Med. Cell. Longev., 2013, 529219.
  28. Jones, D.P. (2008) Radical-free biology of oxidative stress. Am. J. Physiol. Cell Physiol., 295, C849-C868. https://doi.org/10.1152/ajpcell.00283.2008
  29. Kumagai, Y. and Abiko, Y. (2017) Environmental electrophiles: Protein adducts, modulation of redox signaling, and interaction with persulfides/polysulfides. Chem. Res. Toxicol., 30, 203-219. https://doi.org/10.1021/acs.chemrestox.6b00326
  30. Kumagai, Y., Shinkai, Y., Miura, T. and Cho, A.K. (2012) The chemical biology of naphthoquinones and its environmental implications. Annu. Rev. Pharmacol. Toxicol., 52, 221-247. https://doi.org/10.1146/annurev-pharmtox-010611-134517
  31. Sumi, D. (2008) Biological effects of and responses to exposure to electrophilic environmental chemicals. J. Health Sci., 54, 267-272. https://doi.org/10.1248/jhs.54.267
  32. Ahn, S.G. and Thiele, D.J. (2003) Redox regulation of mammalian heat shock factor 1 is essential for Hsp gene activation and protection from stress. Genes Dev., 17, 516-528. https://doi.org/10.1101/gad.1044503
  33. Nishizawa, J., Nakai, A., Matsuda, K., Komeda, M., Ban, T. and Nagata, K. (1999) Reactive oxygen species play an important role in the activation of heat shock factor 1 in ischemic-reperfused heart. Circulation, 99, 934-941. https://doi.org/10.1161/01.CIR.99.7.934
  34. Itoh, K., Tong, K.I. and Yamamoto, M. (2004) Molecular mechanism activating Nrf2-Keap1 pathway in regulation of adaptive response to electrophiles. Free Radic. Biol. Med., 36, 1208-1213. https://doi.org/10.1016/j.freeradbiomed.2004.02.075
  35. Ha, H.L. and Yu, D.Y. (2010) HBx-induced reactive oxygen species activates hepatocellular carcinogenesis via dysregulation of PTEN/Akt pathway. World J. Gastroenterol., 16, 4932-4937. https://doi.org/10.3748/wjg.v16.i39.4932
  36. Tan, P.L., Shavlakadze, T., Grounds, M.D. and Arthur, P.G. (2015) Differential thiol oxidation of the signaling proteins Akt, PTEN or PP2A determines whether Akt phosphorylation is enhanced or inhibited by oxidative stress in C2C12 myotubes derived from skeletal muscle. Int. J. Biochem. Cell Biol., 62, 72-79. https://doi.org/10.1016/j.biocel.2015.02.015
  37. Tonks, N.K. (2003) PTP1B: From the sidelines to the front lines! FEBS Lett., 546, 140-148. https://doi.org/10.1016/S0014-5793(03)00603-3
  38. Lee, S.R., Kwon, K.S., Kim, S.R. and Rhee, S.G. (1998) Reversible inactivation of protein-tyrosine phosphatase 1B in A431 cells stimulated with epidermal growth factor. J. Biol. Chem., 273, 15366-15372. https://doi.org/10.1074/jbc.273.25.15366
  39. Tiganis, T. and Bennett, A.M. (2007) Protein tyrosine phosphatase function: The substrate perspective. Biochem. J., 402, 1-15. https://doi.org/10.1042/BJ20061548
  40. Iwamoto, N., Sumi, D., Ishii, T., Uchida, K., Cho, A.K., Froines, J.R. and Kumagai, Y. (2007) Chemical knockdown of protein-tyrosine phosphatase 1B by 1,2-naphthoquinone through covalent modification causes persistent transactivation of epidermal growth factor receptor. J. Biol. Chem., 282, 33396-33404. https://doi.org/10.1074/jbc.M705224200
  41. Abiko, Y. et al. Personal communication.
  42. Yoshida, E., Kurita, M., Eto, K., Kumagai, Y. and Kaji, T. (2017) Methylmercury promotes prostacyclin release from cultured human brain microvascular endothelial cells via induction of cyclooxygenase-2 through activation of the EGFR-p38 MAPK pathway by inhibiting protein tyrosine phosphatase 1B activity. Toxicology, 392, 40-46. https://doi.org/10.1016/j.tox.2017.09.013
  43. Alam, J., Stewart, D., Touchard, C., Boinapally, S., Choi, A.M. and Cook, J.L. (1999) Nrf2, a Cap'n'Collar transcription factor, regulates induction of the heme oxygenase-1 gene. J. Biol. Chem., 274, 26071-26078. https://doi.org/10.1074/jbc.274.37.26071
  44. Wild, A.C., Moinova, H.R. and Mulcahy, R.T. (1999) Regulation of gamma-glutamylcysteine synthetase subunit gene expression by the transcription factor Nrf2. J. Biol. Chem., 274, 33627-33636. https://doi.org/10.1074/jbc.274.47.33627
  45. Chan, J.Y. and Kwong, M. (2000) Impaired expression of glutathione synthetic enzyme genes in mice with targeted deletion of the Nrf2 basic-leucine zipper protein. Biochim. Biophys. Acta, 1517, 19-26. https://doi.org/10.1016/S0167-4781(00)00238-4
  46. Hayashi, A., Suzuki, H., Itoh, K., Yamamoto, M. and Sugiyama, Y. (2003) Transcription factor Nrf2 is required for the constitutive and inducible expression of multidrug resistance-associated protein 1 in mouse embryo fibroblasts. Biochem. Biophys. Res. Commun., 310, 824-829. https://doi.org/10.1016/j.bbrc.2003.09.086
  47. Vollrath, V., Wielandt, A.M., Iruretagoyena, M. and Chianale, J. (2006) Role of Nrf2 in the regulation of the Mrp2 (ABCC2) gene. Biochem. J., 395, 599-609. https://doi.org/10.1042/BJ20051518
  48. Maher, J.M., Dieter, M.Z., Aleksunes, L.M., Slitt, A.L., Guo, G., Tanaka, Y., Scheffer, G.L., Chan, J.Y., Manautou, J.E., Chen, Y., Dalton, T.P., Yamamoto, M. and Klaassen, C.D. (2007) Oxidative and electrophilic stress induces multidrug resistance-associated protein transporters via the nuclear factor-E2-related factor-2 transcriptional pathway. Hepatology, 46, 1597-1610. https://doi.org/10.1002/hep.21831
  49. Kalthoff, S., Ehmer, U., Freiberg, N., Manns, M.P. and Strassburg, C.P. (2010) Interaction between oxidative stress sensor Nrf2 and xenobiotic-activated aryl hydrocarbon receptor in the regulation of the human phase II detoxifying UDP-glucuronosyltransferase 1A10. J. Biol. Chem., 285, 5993- 6002. https://doi.org/10.1074/jbc.M109.075770
  50. Hirose, R., Miura, T., Sha, R., Shinkai, Y., Tanaka-Kagawa, T. and Kumagai, Y. (2012) A method for detecting covalent modification of sensor proteins associated with 1,4-naphthoquinone-induced activation of electrophilic signal transduction pathways. J. Toxicol. Sci., 37, 891-898. https://doi.org/10.2131/jts.37.891
  51. Abiko, Y., Sha, L., Shinkai, Y., Unoki, T., Luong, N.C., Tsuchiya, Y., Watanabe, Y., Hirose, R., Akaike, T. and Kumagai, Y. (2017) 1,4-Naphthoquinone activates the HSP90/HSF1 pathway through the S-arylation of HSP90 in A431 cells: Negative regulation of the redox signal transduction pathway by persulfides/polysulfides. Free Radic. Biol. Med., 104, 118-128. https://doi.org/10.1016/j.freeradbiomed.2016.12.047
  52. Shinkai, Y., Masuda, A., Akiyama, M., Xian, M. and Kumagai, Y. (2017) Cadmium-mediated activation of the HSP90/HSF1 pathway regulated by reactive persulfides/polysulfides. Toxicol. Sci., 156, 412-421.
  53. Stambolic, V., Suzuki, A., de la Pompa, J.L., Brothers, G.M., Mirtsos, C., Sasaki, T., Ruland, J., Penninger, J.M., Siderovski, D.P. and Mak, T.W. (1998) Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell, 95, 29-39. https://doi.org/10.1016/S0092-8674(00)81780-8
  54. Unoki, T., Abiko, Y., Toyama, T., Uehara, T., Tsuboi, K., Nishida, M., Kaji, T. and Kumagai, Y. (2016) Methylmercury, an environmental electrophile capable of activation and disruption of the Akt/CREB/Bcl-2 signal transduction pathway in SH-SY5Y cells. Sci. Rep., 6, 28944. https://doi.org/10.1038/srep28944
  55. Abiko, Y., Shinkai, Y., Unoki, T., Hirose, R., Uehara, T. and Kumagai, Y. (2017) Polysulfide Na2S4 regulates the activation of PTEN/Akt/CREB signaling and cytotoxicity mediated by 1,4-naphthoquinone through formation of sulfur adducts. Sci. Rep., 7, 4814. https://doi.org/10.1038/s41598-017-04590-z
  56. Unoki, T., Akiyama, M., Kumagai, Y., Goncalves, F.M., Farina, M., da Rocha, J.B.T. and Aschner, M. (2018) Molecular pathways associated with methylmercury-induced Nrf2 modulation. Front. Genet., 9, 373. https://doi.org/10.3389/fgene.2018.00373
  57. Endo, A., Sumi, D., Iwamoto, N. and Kumagai, Y. (2011) Inhibition of DNA binding activity of cAMP response element-binding protein by 1,2-naphthoquinone through chemical modification of Cys-286. Chem. Biol. Interact., 192, 272-277. https://doi.org/10.1016/j.cbi.2011.04.003
  58. Lu, S.C. (2013) Glutathione synthesis. Biochim. Biophys. Acta, 1830, 3143-3153. https://doi.org/10.1016/j.bbagen.2012.09.008
  59. Armstrong, R.N. (1991) Glutathione S-transferases: reaction mechanism, structure, and function. Chem. Res. Toxicol., 4, 131-140. https://doi.org/10.1021/tx00020a001
  60. Eggler, A.L., Liu, G., Pezzuto, J.M., van Breemen, R.B. and Mesecar, A.D. (2005) Modifying specific cysteines of the electrophile-sensing human Keap1 protein is insufficient to disrupt binding to the Nrf2 domain Neh2. Proc. Natl. Acad. Sci. U.S.A., 102, 10070-10075. https://doi.org/10.1073/pnas.0502402102
  61. Ketterer, B., Coles, B. and Meyer, D.J. (1983) The role of glutathione in detoxication. Environ. Health Perspect., 49, 59-69. https://doi.org/10.1289/ehp.834959
  62. Gum, S.I. and Cho, M.K. (2013) Recent updates on acetaminophen hepatotoxicity: the role of nrf2 in hepatoprotection. Toxicol. Res., 29, 165-172. https://doi.org/10.5487/TR.2013.29.3.165
  63. Polhemus, D.J., Calvert, J.W., Butler, J. and Lefer, D.J. (2014) The cardioprotective actions of hydrogen sulfide in acute myocardial infarction and heart failure. Scientifica (Cairo), 2014, 768607.
  64. Polhemus, D.J. and Lefer, D.J. (2014) Emergence of hydrogen sulfide as an endogenous gaseous signaling molecule in cardiovascular disease. Circ. Res., 114, 730-737. https://doi.org/10.1161/CIRCRESAHA.114.300505
  65. Hughes, M.N., Centelles, M.N. and Moore, K.P. (2009) Making and working with hydrogen sulfide: The chemistry and generation of hydrogen sulfide in vitro and its measurement in vivo: a review. Free Radic. Biol. Med., 47, 1346-1353. https://doi.org/10.1016/j.freeradbiomed.2009.09.018
  66. Yoshida, E., Toyama, T., Shinkai, Y., Sawa, T., Akaike, T. and Kumagai, Y. (2011) Detoxification of methylmercury by hydrogen sulfide-producing enzyme in Mammalian cells. Chem. Res. Toxicol., 24, 1633-1635. https://doi.org/10.1021/tx200394g
  67. Ida, T., Sawa, T., Ihara, H., Tsuchiya, Y., Watanabe, Y., Kumagai, Y., Suematsu, M., Motohashi, H., Fujii, S., Matsunaga, T., Yamamoto, M., Ono, K., Devarie-Baez, N.O., Xian, M., Fukuto, J.M. and Akaike, T. (2014) Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling. Proc. Natl. Acad. Sci. U.S.A., 111, 7606-7611. https://doi.org/10.1073/pnas.1321232111
  68. Akaike, T., Ida, T., Wei, F.Y., Nishida, M., Kumagai, Y., Alam, M.M., Ihara, H., Sawa, T., Matsunaga, T., Kasamatsu, S., Nishimura, A., Morita, M., Tomizawa, K., Nishimura, A., Watanabe, S., Inaba, K., Shima, H., Tanuma, N., Jung, M., Fujii, S., Watanabe, Y., Ohmuraya, M., Nagy, P., Feelisch, M., Fukuto, J.M. and Motohashi, H. (2017) Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics. Nat. Commun., 8, 1177. https://doi.org/10.1038/s41467-017-01311-y
  69. Abiko, Y., Yoshida, E., Ishii, I., Fukuto, J.M., Akaike, T. and Kumagai, Y. (2015) Involvement of reactive persulfides in biological bismethylmercury sulfide formation. Chem. Res. Toxicol., 28, 1301-1306. https://doi.org/10.1021/acs.chemrestox.5b00101
  70. Nishida, M., Sawa, T., Kitajima, N., Ono, K., Inoue, H., Ihara, H., Motohashi, H., Yamamoto, M., Suematsu, M., Kurose, H., van der Vliet, A., Freeman, B.A., Shibata, T., Uchida, K., Kumagai, Y. and Akaike, T. (2012) Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration. Nat. Chem. Biol., 8, 714-724. https://doi.org/10.1038/nchembio.1018
  71. Akiyama, M., Shinkai, Y., Unoki, T., Shim, I., Ishii, I. and Kumagai, Y. (2017) The capture of cadmium by reactive polysulfides attenuates cadmium-induced adaptive responses and hepatotoxicity. Chem. Res. Toxicol., 30, 2209-2217. https://doi.org/10.1021/acs.chemrestox.7b00278
  72. Abiko, Y., Ishii, I., Kamata, S., Tsuchiya, Y., Watanabe, Y., Ihara, H., Akaike, T. and Kumagai, Y. (2015) Formation of sulfur adducts of N-acetyl-p-benzoquinoneimine, an electrophilic metabolite of acetaminophen in vivo: Participation of reactive persulfides. Chem. Res. Toxicol., 28, 1796-1802. https://doi.org/10.1021/acs.chemrestox.5b00245