title: Impact of methylmercury exposure on mitochondrial energetics in AC16 and H9C2 cardiomyocytes.
abstract: It has been reported that chronic low dose exposures of methylmercury (MeHg) is associated with cardiovascular diseases in many populations worldwide. The toxic mechanisms through which these adverse effects occur are currently unknown. The objective of this study was to determine the bioenergetic and cytotoxic effects of MeHg on AC16 and H9C2 cardiomyocyte cell lines. Both cell lines exhibit significantly decreased mitochondrial function, cell viability and increased reactive oxygen species (ROS) production. Decreases in maximal respiration and reserve capacity was observed in both cell lines at 1μM. Bioenergetic profile experiments were also performed in tandem with cells exposed to diamide or menadione, compounds which accumulate in mitochondria and disrupt oxidative phosphorylation. AC16 cells show MeHg dose dependant sensitivities with Stateapparent and ATP production values, but H9C2 cells do not show these trends. H9C2 cells may be more resistant to MeHg toxicity than AC16 cells as reflected in the increases of proton leak and Stateapparent. No changes in expression of respiratory complexes were observed. Results suggest that MeHg has the potential to induce cytotoxicity. Furthermore, MeHg may have differential effects on AC16 and H9C2 cells, derived from human and rat cardiac tissue respectively, suggesting that differences in MeHg toxicity may be species-dependent.
authors.affiliation: Center for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Truong
authors.affiliation: Center for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Mailloux
authors.affiliation: Center for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, ON K1N 6N5, Canada. Electronic address: laurie.chan@uottawa.ca.
authors.forename: Hing Man
authors.initials: HM
authors.lastname: Chan
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008767:Methylmercury Compounds / Q000633:toxicity*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D008767:Methylmercury Compounds; D017382:Reactive Oxygen Species; C004925:methylmercuric chloride
keywords: AC16; Bioenergetics; Cardiomyocytes; H9C2; Methylmercury; Mitochondria