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Reactive oxygen species (ROS) mediates the mitochondrial-dependent apoptosis induced by transforming growth factor

B Herrera1, A M Alvarez, A Sánchez

  • 1Departamento de Bioquímica y Biología Molecular, Instituto de Bioquímica, Centro Mixto CSIC/UCM, Madrid, 28040 Madrid, Spain.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|March 22, 2001
PubMed

Insights

Transforming growth factor beta (TGF-beta) triggers apoptosis in fetal hepatocytes by increasing reactive oxygen species (ROS). This ROS production leads to mitochondrial dysfunction and cell death, highlighting a key pathway in apoptosis.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Toxicology

Background:

  • Transforming growth factor beta (TGF-beta) is known to induce apoptosis in various cell types.
  • The precise molecular mechanisms underlying TGF-beta-induced apoptosis in fetal hepatocytes require further elucidation.
  • Reactive oxygen species (ROS) and mitochondrial integrity are critical factors in apoptotic pathways.

Purpose of the Study:

  • To investigate the role of reactive oxygen species (ROS) in TGF-beta-mediated apoptosis of fetal rat hepatocytes.
  • To determine the impact of TGF-beta on mitochondrial transmembrane potential (Deltapsim) and key apoptotic proteins.
  • To explore the involvement of Bcl-2 family proteins, specifically Bcl-xL and Bax, in this apoptotic process.

Main Methods:

  • Fetal rat hepatocytes were treated with TGF-beta.
  • Reactive oxygen species (ROS) content and mitochondrial transmembrane potential (Deltapsim) were analyzed using fluorescent probes, FACScan, and confocal microscopy.
  • Protein and mRNA levels of Bcl-xL and Bax were assessed. Caspase 3 activation and cytochrome c release were measured.

Main Results:

  • TGF-beta treatment led to increased ROS production, preceding the loss of Deltapsim, cytochrome c release, and caspase 3 activation.
  • TGF-beta significantly decreased both protein and mRNA levels of the anti-apoptotic protein Bcl-xL, while Bax levels remained unchanged.
  • Radical scavengers inhibited TGF-beta-induced apoptosis, whereas glutathione synthesis inhibitors exacerbated it, indicating a crucial role for ROS and oxidative stress.

Conclusions:

  • Reactive oxygen species (ROS) play a critical role in mediating TGF-beta-induced apoptosis in fetal hepatocytes.
  • TGF-beta-induced ROS production leads to a decrease in Bcl-xL, mitochondrial dysfunction, and subsequent apoptotic cell death.
  • Targeting ROS pathways may offer therapeutic strategies for conditions involving TGF-beta-induced hepatocyte apoptosis.

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