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Mitochondrial function after bisphenol S exposure: a safe substitute for BPA?
Author(s) -
Singh Radha Dutt,
Easson Sarah,
Thompson Jennifer A.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.08762
Subject(s) - reactive oxygen species , andrology , mitochondrial ros , mitochondrion , oxidative stress , bisphenol s , chemistry , staining , microbiology and biotechnology , biology , bisphenol a , biochemistry , medicine , pathology , organic chemistry , epoxy
Objective Bisphenol A (BPA) is one of the most common industrial chemicals, detected in the urine of 93 percent of US adults. BPA was declared a toxic substance in 2010 and has been linked to metabolic and cardiovascular disease. Amid growing consumer concern, manufacturers increasingly turned to BPA substitutes, the most common of which is bisphenol S (BPS); however, its safety was not determined before introduction to market. Thus, exposure to BPS is on the rise; but its health effects are unclear. Our aim was to determine the impact of BPS exposure on mitochondrial dynamics in vascular smooth muscle cells. Methods Vascular smooth muscle cells (VSMC) were isolated by enzymatic digestion from the thoracic aorta of juvenile (6–7 week old) male C56BL/6 mice. Cells were cultured in DMEM/F12 media supplemented with 10% fetal bovine serum and 1% penicillin‐streptomycin. At 70–80% confluency, cells were treated with vehicle (DMSO) or variable doses of BPS [2.5nM (levels in drinking water); 250nM (permissible limit) and 25μM]. Reactive oxygen species (ROS) levels from cellular and mitochondrial sources were determined by 2′,7′‐dichlorofluorescin diacetate (DCFDA) and MitoSOX staining, respectively. Membrane integrity was assessed by evaluating mitochondrial membrane potential (MMP) by JC1 staining. Mitochondrial fragmentation was measured by MitoTracker Red CMXROS staining and confocal microscopy. Real‐time PCR will be used to measure the expression of genes involved in mito‐fission and fussion and mitochondrial DNA copy number. Results After 30 min and 1 hr of BPS exposure, cellular and mitochondrial ROS levels were increased in a dose‐dependent manner, with a more prominent increase at 1 hr (all doses p<0.001). At 1, 12 and 24 hrs after exposure, mitochondrial depolarization was observed at all doses. At 24 hours, the reduction in mitochondrial membrane potential was greatest at the lowest dose (3‐fold vs. vehicle, p<0.0001). MitoTracker Red CMXROS revealed significant mitochondrial fragmentation at 24 hrs after exposure to 25μM BPS. Conclusion Mitochondrial function is disrupted in VSMCs exposed to BPS at doses lower than the permissible limit and equivalent to human exposure. Studies are underway to determine the mechanistic basis of BPS‐induced mitochondrial dysfunction and long‐term effects on vascular health. Support or Funding Information This study was supported the CIHR, Heart and Stroke Foundation of Canada, and a Kertland Fellowship.