Role of Calcium and Mitochondria in MeHg-mediated Cytotoxicity

Overview

Journal J Biomed Biotechnol

Specialty Biology

Date 2012 Aug 29

PMID 22927718

Citations 22

Authors

Daniel Roos

Rodrigo Seeger

Robson Puntel

Nilda Vargas Barbosa

Affiliations

Soon will be listed here.

Abstract

Methylmercury (MeHg) mediated cytotoxicity is associated with loss of intracellular calcium (Ca²⁺) homeostasis. The imbalance in Ca²⁺ physiology is believed to be associated with dysregulation of Ca²⁺ intracellular stores and/or increased permeability of the biomembranes to this ion. In this paper we summarize the contribution of glutamate dyshomeostasis in intracellular Ca²⁺ overload and highlight the mitochondrial dysfunctions induced by MeHg via Ca²⁺ overload. Mitochondrial disturbances elicited by Ca²⁺ may involve several molecular events (i.e., alterations in the activity of the mitochondrial electron transport chain complexes, mitochondrial proton gradient dissipation, mitochondrial permeability transition pore (MPTP) opening, thiol depletion, failure of energy metabolism, reactive oxygen species overproduction) that could culminate in cell death. Here we will focus on the role of oxidative stress in these phenomena. Additionally, possible antioxidant therapies that could be effective in the treatment of MeHg intoxication are briefly discussed.

Citing Articles

Mitochondrial Dysfunction Plays a Relevant Role in Heart Toxicity Caused by MeHg.

Silva M, Martinez C, Cavalcanti de Albuquerque J, Gouvea A, Freire M, Lauthartte L Toxics. 2024; 12(10).

PMID: 39453132 PMC: 11511492. DOI: 10.3390/toxics12100712.

Should ebselen be considered for the treatment of mercury intoxication? A minireview.

Barbosa N, Aschner M, Tinkov A, Farina M, da Rocha J Toxicol Mech Methods. 2023; 34(1):1-12.

PMID: 37731353 PMC: 10841883. DOI: 10.1080/15376516.2023.2258958.

Effects of low doses of methylmercury (MeHg) exposure on definitive endoderm cell differentiation in human embryonic stem cells.

Li B, Jin X, Chan H Arch Toxicol. 2023; 97(10):2625-2641.

PMID: 37612375 PMC: 10475006. DOI: 10.1007/s00204-023-03580-7.

L-Ascorbic Acid 2-Phosphate Attenuates Methylmercury-Induced Apoptosis by Inhibiting Reactive Oxygen Species Accumulation and DNA Damage in Human SH-SY5Y Cells.

Zuo K, Xu Q, Wang Y, Sui Y, Niu Y, Liu Z Toxics. 2023; 11(2).

PMID: 36851019 PMC: 9967424. DOI: 10.3390/toxics11020144.

Neurotoxicity mechanism of aconitine in HT22 cells studied by microfluidic chip-mass spectrometry.

Zhang Y, Chen S, Fan F, Xu N, Meng X, Zhang Y J Pharm Anal. 2023; 13(1):88-98.

PMID: 36820076 PMC: 9937797. DOI: 10.1016/j.jpha.2022.11.007.

References

Roos D, Puntel R, Santos M, Souza D, Farina M, Nogueira C . Guanosine and synthetic organoselenium compounds modulate methylmercury-induced oxidative stress in rat brain cortical slices: involvement of oxidative stress and glutamatergic system. Toxicol In Vitro. 2009; 23(2):302-7. DOI: 10.1016/j.tiv.2008.12.020. View

Lemasters J, Nieminen A, Qian T, Trost L, Elmore S, Nishimura Y . The mitochondrial permeability transition in cell death: a common mechanism in necrosis, apoptosis and autophagy. Biochim Biophys Acta. 1998; 1366(1-2):177-96. DOI: 10.1016/s0005-2728(98)00112-1. View

Ramanathan G, Atchison W . Ca2+ entry pathways in mouse spinal motor neurons in culture following in vitro exposure to methylmercury. Neurotoxicology. 2011; 32(6):742-50. PMC: 3208762. DOI: 10.1016/j.neuro.2011.07.007. View

Roos D, Puntel R, Lugokenski T, Ineu R, Bohrer D, Burger M . Complex methylmercury-cysteine alters mercury accumulation in different tissues of mice. Basic Clin Pharmacol Toxicol. 2010; 107(4):789-92. DOI: 10.1111/j.1742-7843.2010.00577.x. View

Verity M, Brown W, Cheung M . Organic mercurial encephalopathy: in vivo and in vitro effects of methyl mercury on synaptosomal respiration. J Neurochem. 1975; 25(6):759-66. DOI: 10.1111/j.1471-4159.1975.tb04405.x. View

Duchen M . Mitochondria and Ca(2+)in cell physiology and pathophysiology. Cell Calcium. 2000; 28(5-6):339-48. DOI: 10.1054/ceca.2000.0170. View

Farina M, Dahm K, Schwalm F, Brusque A, Frizzo M, Zeni G . Methylmercury increases glutamate release from brain synaptosomes and glutamate uptake by cortical slices from suckling rat pups: modulatory effect of ebselen. Toxicol Sci. 2003; 73(1):135-40. DOI: 10.1093/toxsci/kfg058. View

Mattson M, Laferla F, Chan S, Leissring M, Shepel P, Geiger J . Calcium signaling in the ER: its role in neuronal plasticity and neurodegenerative disorders. Trends Neurosci. 2000; 23(5):222-9. DOI: 10.1016/s0166-2236(00)01548-4. View

Bennett M, Farnell L, Gibson W . The probability of quantal secretion near a single calcium channel of an active zone. Biophys J. 2000; 78(5):2201-21. PMC: 1300814. DOI: 10.1016/S0006-3495(00)76769-5. View

10.

Budd S, Nicholls D . A reevaluation of the role of mitochondria in neuronal Ca2+ homeostasis. J Neurochem. 1996; 66(1):403-11. DOI: 10.1046/j.1471-4159.1996.66010403.x. View

11.

Yin Z, Jiang H, Syversen T, Rocha J, Farina M, Aschner M . The methylmercury-L-cysteine conjugate is a substrate for the L-type large neutral amino acid transporter. J Neurochem. 2008; 107(4):1083-90. PMC: 2581650. DOI: 10.1111/j.1471-4159.2008.05683.x. View

12.

Morel J, Mironneau J . Effects of phospholipase C inhibitors on Ca2+ channel stimulation and Ca2+ release from intracellular stores evoked by alpha 1A- and alpha 2A-adrenoceptors in rat portal vein myocytes. Biochem Biophys Res Commun. 1996; 218(1):30-4. DOI: 10.1006/bbrc.1996.0006. View

13.

Loew L, Carrington W, Tuft R, Fay F . Physiological cytosolic Ca2+ transients evoke concurrent mitochondrial depolarizations. Proc Natl Acad Sci U S A. 1994; 91(26):12579-83. PMC: 45482. DOI: 10.1073/pnas.91.26.12579. View

14.

Nicholls D, Scott I . The regulation of brain mitochondrial calcium-ion transport. The role of ATP in the discrimination between kinetic and membrane-potential-dependent calcium-ion efflux mechanisms. Biochem J. 1980; 186(3):833-9. PMC: 1161720. DOI: 10.1042/bj1860833. View

15.

Roos D, Puntel R, Farina M, Aschner M, Bohrer D, Rocha J . Modulation of methylmercury uptake by methionine: prevention of mitochondrial dysfunction in rat liver slices by a mimicry mechanism. Toxicol Appl Pharmacol. 2011; 252(1):28-35. PMC: 4917368. DOI: 10.1016/j.taap.2011.01.010. View

16.

Gunter K, GUNTER T . Transport of calcium by mitochondria. J Bioenerg Biomembr. 1994; 26(5):471-85. DOI: 10.1007/BF00762732. View

17.

Pan S, Ryu S, Sheu S . Distinctive characteristics and functions of multiple mitochondrial Ca2+ influx mechanisms. Sci China Life Sci. 2011; 54(8):763-9. PMC: 3214970. DOI: 10.1007/s11427-011-4203-9. View

18.

Shanker G, Aschner M . Methylmercury-induced reactive oxygen species formation in neonatal cerebral astrocytic cultures is attenuated by antioxidants. Brain Res Mol Brain Res. 2003; 110(1):85-91. DOI: 10.1016/s0169-328x(02)00642-3. View

19.

Limke T, Atchison W . Acute exposure to methylmercury opens the mitochondrial permeability transition pore in rat cerebellar granule cells. Toxicol Appl Pharmacol. 2002; 178(1):52-61. DOI: 10.1006/taap.2001.9327. View

20.

de Freitas A, Rocha J . Diphenyl diselenide and analogs are substrates of cerebral rat thioredoxin reductase: a pathway for their neuroprotective effects. Neurosci Lett. 2011; 503(1):1-5. DOI: 10.1016/j.neulet.2011.07.050. View