Gliotoxin induces apoptosis in cultured macrophages via production of reactive oxygen species and cytochrome c release without mitochondrial depolarization |
| |
Authors: | Y. K. Suen K. P. Fung C. Y. Lee S. K. Kong |
| |
Affiliation: | a Department of Biochemistry, The Chinese University of Hong Kong, Hong Kong, China |
| |
Abstract: | The cytotoxicity and its underlying mechanisms induced by gliotoxin (GT), an immunosuppressive agent, in macrophages are poorly understood. We report here that GT induced a rapid apoptosis (DNA fragmentation and hypodiploid nuclei obtained within 4 hrs of treatment) in murine macrophages PU5-1.8 in a dose-dependent and cell cycle-independent manner. The GT-induced apoptosis was suppressed by z-Asp, z-VAD-fmk and antioxidants suggesting that production of reactive oxygen species (ROS) and activation of caspases were important in this process. Also, release of cytochrome c from mitochondria was found to be an early event (within 1 hr) after addition of GT (250 ng/ml) and its presence in the cytosol was sufficient to elicit apoptosis. Interestingly, the release of cytochrome c was not accompanied by a reduction in the mitochondrial membrane potential (ψm) as determined by several ψm-sensitive fluorescent indicators. Taken together, our results indicate that GT is a potent apoptotic agent in PU5-1.8 cells and the loss of ψm is not a universal early marker for apoptosis. |
| |
Keywords: | |
本文献已被 InformaWorld 等数据库收录! |
|