Abstract: FR-PO149

Bisphenol A Is an exogenous Toxin That Promotes Mitochondrial Injury and Death in Tubular Cells

Session Information

  • Mitochondriacs and More
    November 03, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Cell Biology

  • 201 Cell Signaling, Oxidative Stress

Authors

  • Bosch, Enrique, IIS- FJD, Madrid, Spain
  • Ruiz, Alberto, IIS- FJD, Madrid, Spain
  • Civantos, Esther, IIS- FJD, Madrid, Spain
  • Ortiz, Alberto, Fundacion Jimenez Diaz, Madrid, Spain
  • Gonzalez-parra, Emilio E., Fundacion Jimenez Diaz, Madrid, Spain
  • Mas, Sebastian, IIS- FJD, Madrid, Spain
Background

Protein-bound uremix toxins, such a p-Cresol (pC) and metabolites, are harmful chemicals difficult to remove by hemodialysis. Bisphenol A is a ubiquitous environmental toxin, structurally related with pC, that accumulates in CKD, but is not currently considered a uremic toxin. Our aim was to characterize the nephrotoxic potential of BPA. Specifically, we addressed whether it disrupts mitochondrial function and causes cell death in energy demanding cells as tubular cells.

Methods

Experiments were performed on HK-2 human proximal tubular epithelial cells.Cell death and oxidative stress were evaluated by flow cytometry and confocal microscopy in HK-2 human proximal tubular epithelial cells. Functional assays tested ATP, intracellular Ca2+, mitochondrial function (TMRM), oxygen consumption, Nrf2-binding and NAPDH oxidase activity. Gene expression was assessed by qRT-PCR.

Results

Following acute exposure (24h), proximal tubulo-epithelial cell viability is only affected by BPA or pC at concentrations higher than 100 μM. The observed mechanisms are similar for both toxins, since they both promote mitochondrial dysfunction leading to energy depletion, mitochondrial and cytoplasmic oxidative stress (MitoSOX and NAPDH oxidase) and apoptosis in a concentration-dependent manner. An antioxidant response was observed consisting of Nrf2 translocation and increased expression of the Nrf2 target genes Heme oxygenase 1 (HO-1) and NAD(P)H dehydrogenase [quinone] 1 (NQO-1).

Conclusion

This study demonstrates for the first time that BPA causes mitochondrial injury, oxidative stress and apoptotic death in tubular cells. These results characterize BPA as an exogenous toxin that, similar to uremic toxins, may contribute to CKD progression.