Mizoribine-mediated apoptotic signaling pathway in human T-Cell line.
Mizoribine (MZR), an inhibitor of inosine monophosphate dehydrogenase, which depletes cellular guanadine triphosphate, is an immunosuppressive drug. The aim of this study was to evaluate the mechanism by which MZR exerts cytotoxic effects on human Jurkat T cells. Our study showed that MZR-induced apoptotic death of human Jurkat T cells is dose-dependent and time-dependent, as revealed by chromatin condensation and H2AX phosphorylation. Furthermore, MZR increased the catalytic activity of caspase family cysteine proteases, including caspase-3, caspase-8, and caspase-9, in human Jurkat T cells. In conclusion, MZR induces the apoptotic death of human Jurkat T cells via activation of caspase family proteases as well as by mitochondrial dysfunction.
Seo
K W
KW
Division of Transplantation Surgery, Department of Surgery, Chonnam National University Medical School, Gwangju, Korea. sycpvts@chonnam.ac.kr
Lee
H K
HK
Choi
S J N
SJ
So
B J
BJ
Kim
S K
SK
Chung
S Y
SY
D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D019169:Jurkat Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D012263:Ribonucleosides / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D007166:Immunosuppressive Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D012263:Ribonucleosides; D051020:bcl-X Protein; C010052:mizoribine; D020169:Caspases