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Oxygen as an important factor modulating in vitro MeHgCl toxicity associated with mitochondrial genes in hiPSCs.
Augustyniak, J; Lipka, G; Kozlowska, H; Caloni, F; Buzanska, L.
Afiliación
  • Augustyniak J; Department of Neurochemistry, Mossakowski Medical Research Institute Polish Academy of Sciences, Warsaw, Poland.
  • Lipka G; Department of Stem Cell Bioengineering, Mossakowski Medical Research Institute Polish Academy of Sciences, Warsaw, Poland.
  • Kozlowska H; Laboratory of Advanced Microscopy Technique, Mossakowski Medical Research Institute Polish Academy of Sciences, Warsaw, Poland.
  • Caloni F; Department of Environmental Science and Policy (ESP), Università degli Studi di Milano, Milan, Italy.
  • Buzanska L; Department of Stem Cell Bioengineering, Mossakowski Medical Research Institute Polish Academy of Sciences, Warsaw, Poland.
Ecotoxicol Environ Saf ; 241: 113737, 2022 Aug.
Article en En | MEDLINE | ID: mdl-35696963
Mitochondria are energy factories of cells and important targets for methylmercury chloride (MgHgCl). Methylmercury (MeHg) is a well-known environmental toxicant that bioaccumulates in fish and shellfish. It readily crosses the placental barrier, making it a threat to correct fetal development. Despite being comprehensively investigated for years, this compound has not been assessed for its in vitro mitochondrial toxicity under different oxygen conditions. In this study, human induced pluripotent stem cells (hiPSCs) were used to evaluate the dependence of the expression of genes associated with pluripotency and mitochondria on atmospheric (21% O2) and low (5% O2) oxygen concentrations upon MeHgCl treatment. We showed that the toxicity of MeHgCl was strongly related to an increased mtDNA copy number and downregulation of the expression of an mtDNA replication and damage repair-associated gene POLG1 (Mitochondrial Polymerase Gamma Catalytic Subunit) in both tested oxygen conditions. In addition, the viability and mitochondrial membrane potential of hiPSCs were significantly lowered by MeHgCl regardless of the oxygen concentration. However, reactive oxygen species accumulation significantly increased only under atmospheric oxygen conditions; what was associated with increased expression of TFAM (Transcription Factor A, Mitochondrial) and NRF1 (Nuclear Respiratory Factor 1) and downregulation of PARK2 (Parkin RBR E3 Ubiquitin Protein Ligase). Taken together, our results demonstrated that MeHgCl could induce in vitro toxicity in hiPSCs through altering mitochondria-associated genes in an oxygen level-dependent manner. Thus, our work suggests that oxygen should be considered a factor was modulating the in vitro toxicity of environmental pollutants. Typical atmospheric conditions of in vitro culture significantly lower the predictive value of studies of such toxicity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Pluripotentes Inducidas / Compuestos de Metilmercurio Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Female / Humans / Pregnancy Idioma: En Revista: Ecotoxicol Environ Saf Año: 2022 Tipo del documento: Article País de afiliación: Polonia Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Pluripotentes Inducidas / Compuestos de Metilmercurio Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Female / Humans / Pregnancy Idioma: En Revista: Ecotoxicol Environ Saf Año: 2022 Tipo del documento: Article País de afiliación: Polonia Pais de publicación: Países Bajos