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Oxidative stress mediates apoptotic changes induced by hyperglycemia in human tubular kidney cells

Daniela Verzola1, Maria Bianca Bertolotto, Barbara Villaggio

  • 1Division of Nephrology, Department of Internal Medicine, University of Genoa, Genoa, Italy.

Journal of the American Society of Nephrology : JASN
|December 20, 2003
PubMed

Insights

Hyperglycemia increases reactive oxygen species (ROS) and reduces anti-apoptotic protein XIAP in kidney cells, leading to cell death. Elevated ROS predicts this apoptosis, suggesting oxidative stress drives kidney cell damage in high glucose conditions.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Nephrology

Background:

  • Reactive oxygen species (ROS) are key mediators in biological processes, including apoptosis.
  • Hyperglycemia is a hallmark of diabetes and is implicated in diabetic nephropathy.
  • Understanding the mechanisms of hyperglycemia-induced kidney cell injury is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the time course of intracellular ROS production and apoptosis in human kidney proximal tubular cells (HK-2) under hyperglycemic conditions.
  • To examine the expression of apoptosis-related proteins, specifically X chromosome-linked inhibitor of apoptosis protein (XIAP), in response to high glucose.
  • To correlate ROS production with apoptotic changes in HK-2 cells exposed to hyperglycemia.

Main Methods:

  • HK-2 cells were cultured in normal glucose (NG) or high glucose (HG) media for 18–48 hours.
  • Intracellular ROS generation was measured using a fluorescence probe and flow cytometry.
  • Apoptosis was assessed via annexin V binding, and XIAP expression was determined by Western blot.
  • NF-kB binding activity was evaluated using electrophoretic mobility-shift assay.

Main Results:

  • Hyperglycemia significantly increased intracellular ROS production in HK-2 cells.
  • NF-kB binding activity was suppressed, and the expression of the anti-apoptotic protein XIAP was reduced under HG conditions.
  • Significant apoptotic changes were observed in HG-treated cells at 48 hours.
  • Early changes in ROS production at 24 hours were predictive of later apoptotic changes.

Conclusions:

  • Hyperglycemia induces apoptosis in human tubular kidney cells primarily through increased oxidative stress.
  • The downregulation of the anti-apoptotic protein XIAP is a significant component of the hyperglycemic response.
  • ROS production serves as a reliable indicator of subsequent apoptotic cell death in kidney cells under hyperglycemic conditions.

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