title: Role of calcium and mitochondria in MeHg-mediated cytotoxicity.
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.
authors.affiliation: Departamento de Química, CCNE, Programa de Pós-Graduação em Bioquímica Toxicológica, Universidade Federal de Santa Maria, 97105.900 Santa Maria, RS, Brazil.
authors.forename: Daniel
authors.initials: D
authors.lastname: Roos
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Seeger
authors.forename: Robson
authors.initials: R
authors.lastname: Puntel
authors.forename: Nilda
authors.initials: N
authors.lastname: Vargas Barbosa
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008767:Methylmercury Compounds / Q000737:chemistry / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D008767:Methylmercury Compounds; D002118:Calcium