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The UCP2-related mitochondrial pathway participates in rhein-induced apoptosis in HK-2 cells

Yong Mao1,2, Mincheng Zhang1,2, Jiapei Yang1,2

  • 1Department of Clinical Pharmacy , School of Basic Medicine and Clinical Pharmacy , China Pharmaceutical University , Nanjing 211198 , China . Email: maggiejli@126.com ;

Toxicology Research
|August 10, 2018
PubMed

Insights

Rhein induces kidney cell apoptosis through a mitochondrial pathway involving UCP2. This process increases oxidative stress, but antioxidants like NAC can reduce the damage.

Area of Science:

  • Cell Biology
  • Toxicology
  • Biochemistry

Background:

  • Rhein, a key component of total rhubarb anthraquinones (TRAs), is linked to nephrotoxicity.
  • Understanding the specific mechanisms of rhein-induced kidney cell damage is crucial for safety assessments.

Purpose of the Study:

  • To elucidate the mechanism by which rhein induces apoptosis in human renal proximal tubular epithelial cells (HK-2 cells).
  • To investigate the role of the mitochondrial pathway and mitochondrial uncoupling protein 2 (UCP2) in rhein-induced nephrotoxicity.

Main Methods:

  • Annexin V/PI staining assay to detect apoptosis.
  • Assessment of mitochondrial membrane potential (MMP), ATP levels, and cytochrome c (Cyt-c) release.
  • Analysis of Bcl-2 and Bax protein expression.
  • Measurement of reactive oxygen species (ROS) levels and UCP2 expression.
  • Evaluation of the effects of N-acetylcysteine (NAC) and UCP2 inhibition.

Main Results:

  • Rhein treatment induced apoptosis in HK-2 cells.
  • The mitochondria-mediated pathway was identified as critical, evidenced by MMP disruption, decreased ATP, and Cyt-c release.
  • Rhein upregulated Bax and downregulated Bcl-2.
  • Increased ROS levels and inhibited UCP2 expression were observed.
  • UCP2 inhibition exacerbated rhein-induced apoptosis, while NAC treatment attenuated it.

Conclusions:

  • Rhein induces apoptosis in HK-2 cells via the UCP2-related mitochondrial pathway.
  • Rhein may act as a weak inhibitor of UCP2, contributing to oxidative stress and apoptosis.
  • UCP2 plays a significant role in the mitochondrial apoptotic pathway, and its modulation impacts rhein-induced kidney cell injury.

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