Top

Environmental Health and Preventive Medicine

Published in:

Open Access 01-12-2020 | Review article

Methylmercury toxic mechanism related to protein degradation and chemokine transcription

Authors: Jin-Yong Lee, Gi-Wook Hwang, Akira Naganuma, Masahiko Satoh

Published in: Environmental Health and Preventive Medicine | Issue 1/2020

Abstract

Methylmercury is an environmental pollutant that causes neurotoxicity. Recent studies have reported that the ubiquitin-proteasome system is involved in defense against methylmercury toxicity through the degradation of proteins synthesizing the pyruvate. Mitochondrial accumulation of pyruvate can enhance methylmercury toxicity. In addition, methylmercury exposure induces several immune-related chemokines, specifically in the brain, and may cause neurotoxicity. This summary highlights several molecular mechanisms of methylmercury-induced neurotoxicity.

Harada M. Minamata disease: methylmercury poisoning in Japan caused by environmental pollution. Crit Rev Toxicol. 1995;25:1–24. https://doi.org/10.3109/10408449509089885.CrossRefPubMed

Randall PM, Chattopadhyay S. Mercury contaminated sediment sites-an evaluation of remedial options. Environ Res. 2013;125:131–49. https://doi.org/10.1016/j.envres.2013.01.007.CrossRefPubMed

Harding G, Dalziel J, Vass P. Bioaccumulation of methylmercury within the marine food web of the outer Bay of Fundy, Gulf of Maine. PLoS One. 2018;13:e0197220. https://doi.org/10.1371/journal.pone.0197220.CrossRefPubMedPubMedCentral

Clarkson TW. The three modern faces of mercury. Environ Health Perspect. 2002;110(Suppl 1):11–23. https://doi.org/10.1289/ehp.02110s111.CrossRefPubMedPubMedCentral

Risher JF, Murray HE, Prince GR. Organic mercury compounds: human exposure and its relevance to public health. Toxicol Ind Health. 2002;18:109–60. https://doi.org/10.1191/0748233702th138oa.CrossRefPubMed

Clarkson TW, Magos L. The toxicology of mercury and its chemical compounds. Crit Rev Toxicol. 2006;36:609–62. https://doi.org/10.1080/10408440600845619.CrossRef

Cernichiari E, Brewer R, Myers GJ, Marsh DO, Lapham LW, Cox C, et al. Monitoring methylmercury during pregnancy: maternal hair predicts fetal brain exposure. Neurotoxicology. 1995;16:705–10.PubMed

Clarkson TW, Magos L, Myers GJ. The toxicology of mercury--current exposures and clinical manifestations. N Engl J Med. 2003;349:1731–7. https://doi.org/10.1056/NEJMra022471.CrossRefPubMed

Clarkson TW. The toxicology of mercury. Crit Rev Clin Lab Sci. 1997;34:369–403. https://doi.org/10.3109/10408369708998098.CrossRefPubMed

10.

Murata K, Dakeishi M, Shimada M, Satoh H. Assessment of intrauterine methylmercury exposure affecting child development: messages from the newborn. Tohoku J Exp Med. 2007;213:187–202. https://doi.org/10.1620/tjem.213.187.CrossRefPubMed

11.

Freitas AJ, Rocha JB, Wolosker H, Souza DO. Effects of Hg2+ and CH3Hg + on Ca2+ fluxes in rat brain microsomes. Brain Res. 1996;738:257–64. https://doi.org/10.1016/s0006-8993(96)00781-0.CrossRefPubMed

12.

Aschner M, Syversen T, Souza DO, Rocha JB, Farina M. Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity. Braz J Med Biol Res. 2007;40:285–91. https://doi.org/10.1590/s0100-879x2007000300001.CrossRefPubMed

13.

Tuite MF. Yeast models of neurodegenerative diseases. Prog Mol Biol Transl Sci. 2019;168:351–79. https://doi.org/10.1016/bs.pmbts.2019.07.001.CrossRefPubMed

14.

Furuchi T, Hwang GW, Naganuma A. Overexpression of the ubiquitin-conjugating enzyme Cdc34 confers resistance to methylmercury in Saccharomyces cerevisiae. Mol Pharmacol. 2002;61:738–41. https://doi.org/10.1124/mol.61.4.738.CrossRef

15.

Hwang GW, Furuchi T, Naganuma A. A ubiquitin-proteasome system is responsible for the protection of yeast and human cells against methylmercury. FASEB J. 2002;16:709–11. https://doi.org/10.1096/fj.01-0899fje.CrossRefPubMed

16.

Goebl MG, Yochem J, Jentsch S, McGrath JP, Varshavsky A, Byers B. The yeast cell cycle gene CDC34 encodes a ubiquitin-conjugating enzyme. Science. 1988;241:1331–5. https://doi.org/10.1126/science.2842867.CrossRefPubMed

17.

Skowyra D, Craig KL, Tyers M, Elledge SJ, Harper JW. F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex. Cell. 1997;91:209–19. https://doi.org/10.1016/s0092-8674(00)80403-1.CrossRefPubMed

18.

Hwang GW, Ishida Y, Naganuma A. Identification of F-box proteins that are involved in resistance to methylmercury in Saccharomyces cerevisiae. FEBS Lett. 2006;580:6813–8. https://doi.org/10.1016/j.febslet.2006.11.045.CrossRefPubMed

19.

Lee JY, Ishida Y, Kuge S, Naganuma A, Hwang GW. Identification of substrates of F-box protein involved in methylmercury toxicity in yeast cells. FEBS Lett. 2015;589:2720–5. https://doi.org/10.1016/j.febslet.2015.08.016.CrossRefPubMed

20.

Chelstowska A, Liu Z, Jia Y, Amberg D, Butow RA. Signalling between mitochondria and the nucleus regulates the expression of a new D-lactate dehydrogenase activity in yeast. Yeast. 1999;15:1377–91. https://doi.org/10.1002/(sici)1097-0061(19990930)15:13<1377::Aid-yea473>3.0.Co;2-0.CrossRefPubMed

21.

McAlister L, Holland MJ. Targeted deletion of a yeast enolase structural gene. Identification and isolation of yeast enolase isozymes. J Biol Chem. 1982;257:7181–8.PubMed

22.

Fraenkel DG. The top genes: on the distance from transcript to function in yeast glycolysis. Curr Opin Microbiol. 2003;6:198–201. https://doi.org/10.1016/s1369-5274(03)00023-7.CrossRefPubMed

23.

Lee JY, Ishida Y, Takahashi T, Naganuma A, Hwang GW. Transport of pyruvate into mitochondria is involved in methylmercury toxicity. Sci Rep. 2016;6:21528. https://doi.org/10.1038/srep21528.CrossRefPubMedPubMedCentral

24.

Hwang GW, Lee JY, Ryoke K, Matsuyama F, Kim JM, Takahashi T, et al. Gene expression profiling using DNA microarray analysis of the cerebellum of mice treated with methylmercury. J Toxicol Sci. 2011;36:389–91. https://doi.org/10.2131/jts.36.389.CrossRefPubMed

25.

Rostene W, Kitabgi P, Parsadaniantz SM. Chemokines: a new class of neuromodulator? Nat Rev Neurosci. 2007;8:895–903. https://doi.org/10.1038/nrn2255.CrossRefPubMed

26.

Lee JY, Hwang GW, Kim MS, Takahashi T, Naganuma A. Methylmercury induces a brain-specific increase in chemokine CCL4 expression in mice. J Toxicol Sci. 2012;37:1279–82. https://doi.org/10.2131/jts.37.1279.CrossRefPubMed

27.

Kim MS, Takahashi T, Lee JY, Hwang GW, Naganuma A. Global chemokine expression in methylmercury-treated mice: methylmercury induces brain-specific expression of CCL3 and CCL4. J Toxicol Sci. 2013;38:925–9. https://doi.org/10.2131/jts.38.925.CrossRefPubMed

28.

Kim MS, Takahashi T, Lee JY, Hwang GW, Naganuma A. Methylmercury induces CCL2 expression through activation of NF-kappaB in human 1321 N1 astrocytes. J Toxicol Sci. 2012;37:1275–8. https://doi.org/10.2131/jts.37.1275.CrossRefPubMed

29.

Kim M-S, Takahashi T, Lee J-Y, Toyama T, Hoshi T, Kuge S, et al. Methylmercury induces the expression of chemokine CCL4 via SRF activation in C17.2 mouse neural stem cells. Sci Rep. 2019;9:4631. https://doi.org/10.1038/s41598-019-41127-y.CrossRefPubMedPubMedCentral

30.

Mergenthaler P, Lindauer U, Dienel GA, Meisel A. Sugar for the brain: the role of glucose in physiological and pathological brain function. Trends Neurosci. 2013;36:587–97. https://doi.org/10.1016/j.tins.2013.07.001.CrossRefPubMedPubMedCentral

31.

Gorter JA, van Vliet EA, Aronica E, Breit T, Rauwerda H, Lopes da Silva FH, et al. Potential new antiepileptogenic targets indicated by microarray analysis in a rat model for temporal lobe epilepsy. J Neurosci. 2006;26:11083–110. https://doi.org/10.1523/jneurosci.2766-06.2006.CrossRefPubMedPubMedCentral

32.

Shimizu H, Bolati D, Higashiyama Y, Nishijima F, Shimizu K, Niwa T. Indoxyl sulfate upregulates renal expression of MCP-1 via production of ROS and activation of NF-kappaB, p53, ERK, and JNK in proximal tubular cells. Life Sci. 2012;90:525–30. https://doi.org/10.1016/j.lfs.2012.01.013.CrossRefPubMed

33.

Gamo K, Kiryu-Seo S, Konishi H, Aoki S, Matsushima K, Wada K, et al. G-protein-coupled receptor screen reveals a role for chemokine receptor CCR5 in suppressing microglial neurotoxicity. J Neurosci. 2008;28:11980–8. https://doi.org/10.1523/jneurosci.2920-08.2008.CrossRefPubMedPubMedCentral

34.

Lee JY, Tokumoto M, Hwang GW, Lee MY, Satoh M. Identification of ARNT-regulated BIRC3 as the target factor in cadmium renal toxicity. Sci Rep. 2017;7:17287. https://doi.org/10.1038/s41598-017-17494-9.CrossRefPubMedPubMedCentral

35.

Sarma SN, Saleem A, Lee JY, Tokumoto M, Hwang GW, Man Chan H, et al. Effects of long-term cadmium exposure on urinary metabolite profiles in mice. J Toxicol Sci. 2018;43:89–100. https://doi.org/10.2131/jts.43.89.CrossRefPubMed

Title: Methylmercury toxic mechanism related to protein degradation and chemokine transcription
Authors: Jin-Yong Lee
Gi-Wook Hwang
Akira Naganuma
Masahiko Satoh
Publication date: 01-12-2020
Publisher: BioMed Central
Published in: Environmental Health and Preventive Medicine / Issue 1/2020
Print ISSN: 1342-078X
Electronic ISSN: 1347-4715
DOI: https://doi.org/10.1186/s12199-020-00868-3

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Methylmercury toxic mechanism related to protein degradation and chemokine transcription

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2020

Multidisciplinary approach to assess the toxicities of arsenic and barium in drinking water

Changes in smoking behavior among victims after the great East Japan earthquake and tsunami

Identification by TCGA database search of five genes that are aberrantly expressed and involved in hepatocellular carcinoma potentially via DNA methylation changes

Associations of socioeconomic status and lifestyle factors with dental neglect of elementary school children: the MEXT Super Shokuiku School Project

Association between metal cobalt exposure and the risk of congenital heart defect occurrence in offspring: a multi-hospital case-control study

Lifestyle interventions in the maritime settings: a systematic review