2,4-Dinitrophenol induces apoptosis in As4.1 juxtaglomerular cells through rapid depletion of GSH

Cell Biol Int. 2008 Dec;32(12):1536-45. doi: 10.1016/j.cellbi.2008.08.023. Epub 2008 Aug 30.

Abstract

2,4-Dinitrophenol (DNP) is an uncoupler of oxidative phosphorylation in mitochondria. Here, we investigated the in vitro effect of DNP on apoptosis and the involvement of reactive oxygen species (ROS) in As4.1 juxtaglomerular cell death. Dose- and time-dependent induction of apoptosis was evidenced by flow cytometric detection of sub-G1 DNA content and annexin V binding assay. The intracellular H(2)O(2) and O(2)(-) levels were markedly increased in DNP-treated cells. However, the reduction of intracellular H(2)O(2) level by Tiron and catalase did not prevent apoptosis induced by DNP. Moreover, DNP rapidly reduced intracellular GSH content in As4.1 cells. Taken together, apoptosis in DNP-treated As4.1 cells is correlated with the rapid change of intracellular GSH levels rather than ROS levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,4-Dinitrophenol / toxicity*
  • Animals
  • Annexin A5 / metabolism
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Cell Line, Tumor
  • DNA / analysis
  • DNA / metabolism
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Glutathione / metabolism*
  • Juxtaglomerular Apparatus / drug effects*
  • Juxtaglomerular Apparatus / metabolism
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Oxidative Phosphorylation / drug effects
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Reactive Oxygen Species / metabolism
  • Time Factors
  • Uncoupling Agents / toxicity
  • Up-Regulation / drug effects
  • Up-Regulation / physiology

Substances

  • Annexin A5
  • Reactive Oxygen Species
  • Uncoupling Agents
  • DNA
  • Glutathione
  • 2,4-Dinitrophenol