Selenium protection against mercury neurotoxicity: Modulation of apoptosis and autophagy in the anterior pituitary

Asar, Hoda Mahmoud El; Mohammed, Enas Ahmed; Aboulhoda, Basma Emad; Emam, H.; Imam, Ahmad Abdel-Aliem

doi:10.1016/j.lfs.2019.116578

Cited by 34 publications

(15 citation statements)

References 39 publications

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“…Another possible mechanism is the modulation of autophagy and apoptosis. We observed that MeHg treatment caused a decrease in autophagy, indicated by a lower LC3BII/LC3BI ratio and higher protein expression of p62 with the increase in apoptosis, as reported in the anterior pituitary of rats ( El Asar et al. 2019 ).…”

Section: Discussionsupporting

confidence: 81%

Characterizing the Low-Dose Effects of Methylmercury on the Early Stages of Embryo Development Using Cultured Human Embryonic Stem Cells

Bai

Qiao

Jin

et al. 2021

Environ Health Perspect

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Background: Global concerns of methylmercury (MeHg) exposure have been raised, especially on its effects on pregnant women. Recent epidemiological studies have revealed associations between maternal blood/hair MeHg concentrations, adverse pregnancy outcomes, and developmental deficits. However, the underlying mechanisms remain unclear. Objectives: In this study, we characterized the effects of MeHg exposure on undifferentiated human embryonic stem cells (hESCs) and extrapolated the effects to human embryonic development. Methods: hESCs were exposed to 0, 1, 5, 10, 50, 100 or MeHg for 24 h or 6 d. Cell adherence and colony formation and expansion were examined under the microscope. Cell attachment, viability/proliferation, apoptosis, stress response, cell cycle, autophagy, and expression of cell lineage marker genes and proteins were measured at the end of exposures. Results: Our results indicated that exposure to nanomolar concentrations of MeHg was associated with a ) higher levels of reactive oxygen species (ROS) and hemeoxygenase-1 (HO-1), suggesting increased stress and adaptive responses; b ) lower cellular adhesion, viability/proliferation, and colony formation and expansion; c ) higher levels of apoptosis, reflected by higher cleaved caspase-3 expression and Annexin V binding; d ) higher levels of cytoskeleton protein expression; e ) higher rates of G1/S phase cell cycle arrest; and f ) autophagy inhibition, as shown by a lower LC3BII/LC3BI ratio and accumulation of SQSTM1 (p62). These outcomes were accompanied by higher expressions of self-renewal genes or proteins or both, including OCT4, SOX2, NANOG, and cytokine receptor IL6ST, as well as pluripotency and the cell fate regulator cyclin D1. Discussion: These results revealed that under the selection pressure of exposure to low doses of MeHg, some hESCs underwent apoptosis, whereas others adapted and survived with enhanced self-renewal gene expression and specific morphological phenotypes. Findings from the present study provide in vitro evidence that low doses of MeHg adversely affect hESCs when exposed during a period of time that models embryonic pre-, during, and early postimplantation stages. https://doi.org/10.1289/EHP7349

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Section: Discussionsupporting

confidence: 81%

Characterizing the Low-Dose Effects of Methylmercury on the Early Stages of Embryo Development Using Cultured Human Embryonic Stem Cells

Bai

Qiao

Jin

et al. 2021

Environ Health Perspect

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“…Although low concentrations of mercury increase autophagy by regulating p53 and DRAM (Chatterjee et al, 2014), long‐term exposure to medium‐and high‐dose mercury damages the cytoplasm, nucleus, mitochondria, and lysosomes, including cell death (Bjorklund et al, 2019; Jia et al, 2015). Mercury poisoning leads to autophagy disorders, which can be improved by selenium (El Asar et al, 2019), and promotes apoptosis of adenohypophysis cells (El Asar et al, 2019).…”

Section: Regulation Of Autophagy By Other Metalsmentioning

confidence: 99%

Transition metals and metal complexes in autophagy and diseases

Luo

Huang

et al. 2021

Journal Cellular Physiology

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Transition metals refer to the elements in the d and ds blocks of the periodic table. Since the success of cisplatin and auranofin, transition metal‐based compounds have become a prospective source for drug development, particularly in cancer treatment. In recent years, extensive studies have shown that numerous transition metal‐based compounds could modulate autophagy, promising a new therapeutic strategy for metal‐related diseases and the design of metal‐based agents. Copper, zinc, and manganese, which are common components in physiological pathways, play important roles in the progression of cancer, neurodegenerative diseases, and cardiovascular diseases. Furthermore, enrichment of copper, zinc, or manganese can regulate autophagy. Thus, we summarized the current advances in elucidating the mechanisms of some metals/metal‐based compounds and their functions in autophagy regulation, which is conducive to explore the intricate roles of autophagy and exploit novel therapeutic drugs for human diseases.

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“…One possible explanation for this finding could be that exposure to MeHg-Cys inhibits or causes degradation of the autophagic machinery. Some previous studies, using in vitro and in vivo models, reported a reduction in autophagy following exposure to MeHg [ 43 , 44 ], while other studies have shown that exposure to low doses of MeHg enhances autophagy [ 45 ]. These reported differences may be due to variations among the cell types studied, differences in the concentrations of MeHg used for the study, and the exposure time for each study.…”

Section: Discussionmentioning

confidence: 99%

Transport and Toxicity of Methylmercury-Cysteine in Cultured BeWo Cells

Ganapathy

Farrell

Vaghela

et al. 2021

IJMS

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Mercury is a heavy metal toxicant that is prevalent throughout the environment. Organic forms of mercury, such as methylmercury (MeHg), can cross the placenta and can lead to lasting detrimental effects in the fetus. The toxicological effects of MeHg on the placenta itself have not been clearly defined. Therefore, the purpose of the current study was to assess the transport of MeHg into placental syncytiotrophoblasts and to characterize the mechanisms by which MeHg exerts its toxic effects. Cultured placental syncytiotrophoblasts (BeWo) were used for these studies. The transport of radioactive MeHg was measured to identify potential mechanisms involved in the uptake of this compound. The toxicological effects of MeHg on BeWo cells were determined by assessing visible pathological change, autophagy, mitochondrial viability, and oxidative stress. The findings of this study suggest that MeHg compounds are transported into BeWo cells primarily by sodium-independent amino acid carriers and organic anion transporters. The MeHg altered mitochondrial function and viability, decreased mitophagy and autophagy, and increased oxidative stress. Exposure to higher concentrations of MeHg inhibited the ability of cells to protect against MeHg-induced injury. The findings show that MeHg is directly toxic to syncytiotrophoblasts and may lead to disruptions in the fetal/maternal transfer of nutrients and wastes.

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Selenium protection against mercury neurotoxicity: Modulation of apoptosis and autophagy in the anterior pituitary

Cited by 34 publications

References 39 publications

Characterizing the Low-Dose Effects of Methylmercury on the Early Stages of Embryo Development Using Cultured Human Embryonic Stem Cells

Characterizing the Low-Dose Effects of Methylmercury on the Early Stages of Embryo Development Using Cultured Human Embryonic Stem Cells

Transition metals and metal complexes in autophagy and diseases

Transport and Toxicity of Methylmercury-Cysteine in Cultured BeWo Cells

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