Biomol Ther.  2013 Sep;21(5):358-363.

Glutathione Depletion by L-Buthionine-S,R-Sulfoximine Induces Apoptosis of Cardiomyocytes through Activation of PKC-delta

  • 1Department of Pathophysiology, College of Pharmacy, Ajou University, Suwon 443-749, Republic of Korea.
  • 2Brain Korea 21 for Molecular Science and Technology, Ajou University, Suwon 443-749, Republic of Korea.
  • 3Research Institute of Pharmaceutical Sciences and Technology, Ajou University, Suwon 443-749, Republic of Korea.


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.


Glutathione; Reactive oxygen species; H9c2; Cell death; PKC-delta
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