Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Glutathione Depletion by L-Buthionine-S,R-Sulfoximine Induces Apoptosis of Cardiomyocytes through Activation of PKC-δ

  • Kim, Young-Ae (Department of Pathophysiology, College of Pharmacy) ;
  • Kim, Mi-Young (Department of Pathophysiology, College of Pharmacy) ;
  • Jung, Yi-Sook (Department of Pathophysiology, College of Pharmacy)
  • Received : 2013.09.02
  • Accepted : 2013.09.23
  • Published : 2013.09.30
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Abstract

In the present study, we investigated the effect of intracellular glutathione (GSH) depletion in heart-derived H9c2 cells and its mechanism. L-buthionine-S,R-sulfoximine (BSO) induced the depletion of cellular GSH, and BSO-induced reactive oxygen species (ROS) production was inhibited by glutathione monoethyl ester (GME). Additionally, GME inhibited BSO-induced caspase-3 activation, annexin V-positive cells, and annexin V-negative/propidium iodide (PI)-positive cells. Treatment with rottlerin completely blocked BSO-induced cell death and ROS generation. BSO-induced GSH depletion caused a translocation of PKC-${\delta}$ from the cytosol to the membrane fraction, which was inhibited by treatment with GME. From these results, it is suggested that BSO-induced depletion of cellular GSH causes an activation of PKC-${\delta}$ and, subsequently, generation of ROS, thereby inducing H9c2 cell death.

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References

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