Roos Daniel, Seeger Rodrigo, Puntel Robson, Vargas Barbosa Nilda
Departamento de Química, CCNE, Programa de Pós-Graduação em Bioquímica Toxicológica, Universidade Federal de Santa Maria, 97105.900 Santa Maria, RS, Brazil.
J Biomed Biotechnol. 2012;2012:248764. doi: 10.1155/2012/248764. Epub 2012 Jul 3.
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.
甲基汞(MeHg)介导的细胞毒性与细胞内钙(Ca²⁺)稳态的丧失有关。Ca²⁺生理失衡被认为与Ca²⁺细胞内储存的失调和/或生物膜对该离子的通透性增加有关。在本文中,我们总结了谷氨酸稳态失衡在细胞内Ca²⁺过载中的作用,并强调了MeHg通过Ca²⁺过载诱导的线粒体功能障碍。Ca²⁺引起的线粒体紊乱可能涉及多个分子事件(即线粒体电子传递链复合物活性改变、线粒体质子梯度耗散、线粒体通透性转换孔(MPTP)开放、硫醇耗竭、能量代谢失败、活性氧过度产生),这些事件最终可能导致细胞死亡。在此,我们将重点关注氧化应激在这些现象中的作用。此外,还简要讨论了可能有效治疗MeHg中毒的抗氧化疗法。