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

• Kim YA
• Kim MY
• Jung YS

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.

Keyword

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

MeSH Terms

Apoptosis*
Caspase 3
Cell Death
Cytosol
Glutathione*
Membranes
Myocytes, Cardiac*
Reactive Oxygen Species
Caspase 3
Glutathione
Reactive Oxygen Species