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Acetyl-L-carnitine suppresses apoptosis of thioredoxin 2-deficient DT40 cells

Xiaoping Zhu1, Eisuke F Sato, Yi Wang

  • 1Department of Biochemistry & Molecular Pathology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno, Osaka 545-8585, Japan.

Archives of Biochemistry and Biophysics
|August 21, 2008
PubMed

Insights

Acetyl-L-carnitine prevents mitochondria-dependent apoptosis by suppressing oxidative stress. This occurs through inhibiting reactive oxygen species and protecting adenine nucleotide translocator (ANT) in cells lacking TRX2.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Mitochondrial Function

Background:

  • Mitochondria-dependent apoptosis is a critical cellular process.
  • Thioredoxin 2 (TRX2) plays a role in protecting cells from oxidative stress.
  • L-carnitine and its metabolites are known to influence cellular metabolism.

Purpose of the Study:

  • To investigate the mechanism by which L-carnitine metabolites inhibit mitochondria-dependent apoptosis.
  • To elucidate the role of TRX2 in regulating apoptosis and oxidative stress.
  • To compare apoptotic pathways in wild-type and TRX2-knockout cells.

Main Methods:

  • Utilized conditional TRX2-knockout DT40 cells (TRX2(-/-)) and wild-type cells.
  • Assessed caspase activation (caspase-3, -9, -8).
  • Measured reactive oxygen species (ROS) and glutathione levels.
  • Examined oxidation and binding of adenine nucleotide translocator (ANT).
  • Monitored release of cytochrome c and SOD1 from mitochondria.

Main Results:

  • TRX2(-/-) cells exhibited strong caspase-3 and -9 activation, increased ROS, and decreased glutathione.
  • Critical thiol groups of ANT were more easily oxidized in TRX2(-/-) cells.
  • Reduced ANT selectively bound to TRX2.
  • Cytochrome c and SOD1 were released more readily from mitochondria in TRX2(-/-) cells.
  • Acetyl-L-carnitine, but not L-carnitine, inhibited these apoptosis-related phenomena.

Conclusions:

  • Acetyl-L-carnitine effectively suppresses mitochondrial oxidative stress.
  • This suppression prevents the activation of the mitochondrial apoptosis signaling pathway.
  • TRX2 plays a crucial role in protecting against oxidative stress-induced apoptosis via ANT regulation.

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