Mitochondria-regulated death pathway mediates (DIPP-L-Leu)2-L-LysOCH3-induced K562 cells apoptosis.
(DIPP-L-Leu)2-L-LysOCH3 is a diisopropylphosphoryl dipeptide which is known to induce apoptosis of human leukemia K562 cells. The molecular and cellular mechanisms involved in this process remain to be clarified. Herein, we show that (DIPP-L-Leu)2-L-LysOCH3-induced apoptosis is associated with cytosolic accumulation of cytochrome c, sustained loss of mitochondrial transmembrane potential (MMP), transient generation of reactive oxygen species (ROS) and elevation of intracellular Ca2+ concentration. A specific caspase assay reveals an increase in caspase-9 and caspase-3 activity but no change in caspase-8 activity. Immunofluorescence analysis indicates that (DIPP-L-Leu)2-L-LysOCH3 induced upregulation of pro-apoptotic Bax and downregulation of anti-apoptotic Bcl-2 and Bcl-x(L). These results suggest that the mitochondria-regulated death pathway mediates (DIPP-L-Leu)2-L-LysOCH3-induced K562 cells apoptosis.
The Key Laboratory of Chemical Biology, Guangdong Province, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055 P. R. China.
Jie
J
Yang
Yuyang
Y
Jiang
Feng
F
Liu
Yufen
Y
Zhao
D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002413:Cations, Divalent / Q000737:chemistry; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004151:Dipeptides / Q000737:chemistry / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D015394:Molecular Structure; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
C470516:(DIPP-L-Leu)2-L-Lys-OCH3; D002413:Cations, Divalent; D004151:Dipeptides; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D045304:Cytochromes c; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D020782:Matrix Metalloproteinases; D002118:Calcium