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Updated: Oct 26, 2025
Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
Published on: January 7, 2013
BDE-47 induces nephrotoxicity through ROS-dependent pathways of mitochondrial dynamics in PK15 cells
Shiyao Sun1, Zhihui Zhao1, Qinxiong Rao1
1Institute for Agri-Food Standards and Testing Technology, Shanghai Academy of Agricultural Sciences, Shanghai 201403, China.
Abstract:
2,2',4,4'-tetrabromodiphenyl ether (BDE-47)-induced nephrotoxicity is closely associated with oxidative stresses and mitochondrial abnormalities. Mitochondrial fusion and fission dynamics are crucial for maintaining mitochondrial and cellular physiological homeostasis. However, the detailed mechanisms through which BDE-47 disrupts this dynamic and contributes to renal injuries are still not fully understood. The porcine kidney-15 (PK15) cell line, a well-defined in vitro animal renal toxicological model, was exposed to BDE-47 with concentrations of 12.5, 25, 50, and 100 μM, respectively. Cell viability, the levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP), the mitochondrial membrane potential (MMP), and the expression levels of key mitochondrial fusion and fission proteins were assessed. BDE-47 reduced cell viability and disrupted mitochondrial dynamics by inhibiting mitochondrial fusion and fission simultaneously, leading to MMP decreases, ROS overgeneration, ATP depletion, and cellular disintegration in a dose-dependent manner. Additionally, the mitochondrial division inhibitor (Mdivi-1) with the concentration of 20 μM observed to restore the downregulation of mitochondrial fusion and fission proteins, alleviate damages in mitochondrial morphology and functionality, correct ROS overproduction, and enable cell survival. The antioxidant N-acety-L-cysteine (NAC) with the concentration of 1 mM also simultaneously reversed the imbalance of mitochondrial dynamics, decreased ROS production, and restored mitochondrial morphology in PK15 cells exposed to BDE-47. Our data provide new insights indicating that BDE-47 disrupts mitochondrial fusion/fission dynamics to induce mitochondrial abnormalities, triggering oxidative stresses and thus contributing to PK15 cell dysfunction. ROS-dependent pathways in mitochondrial dynamics may provide a new avenue for developing effective strategies to protect cells against BDE-47-induced nephrotoxicity.
Insights
2,2
Area of Science:
- Toxicology
- Cell Biology
- Mitochondrial Dynamics
Background:
- 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) causes nephrotoxicity linked to oxidative stress and mitochondrial issues.
- Mechanisms of BDE-47's disruption of mitochondrial dynamics in renal cells remain unclear.
Purpose of the Study:
- To investigate how BDE-47 affects mitochondrial fusion and fission dynamics in porcine kidney-15 (PK15) cells.
- To explore potential therapeutic strategies against BDE-47-induced nephrotoxicity.
Main Methods:
- PK15 cells were exposed to varying concentrations of BDE-47.
- Assessed cell viability, reactive oxygen species (ROS), adenosine triphosphate (ATP), mitochondrial membrane potential (MMP), and mitochondrial protein expression.
- Utilized mitochondrial division inhibitor (Mdivi-1) and N-acetyl-L-cysteine (NAC) as potential protective agents.
Main Results:
- BDE-47 inhibited both mitochondrial fusion and fission, leading to decreased cell viability, MMP, and ATP levels, alongside increased ROS.
- Mdivi-1 and NAC treatments reversed BDE-47-induced mitochondrial dysfunction, reduced ROS, and improved cell survival.
- BDE-47 disrupted mitochondrial dynamics in a dose-dependent manner.
Conclusions:
- BDE-47 induces nephrotoxicity by disrupting mitochondrial fusion/fission dynamics, causing mitochondrial abnormalities and oxidative stress.
- Targeting ROS-dependent pathways in mitochondrial dynamics offers a potential therapeutic approach for BDE-47-induced kidney damage.
