Peer-Reviewed Journal Details
Mandatory Fields
England, K,Driscoll, CO,Cotter, TG;
2006
June
Free Radical Research
ROS and protein oxidation in early stages of cytotoxic drug induced apoptosis
Validated
()
Optional Fields
post-translational modifications proteomics apoptosis carbonylation ER stress leukaemia DISULFIDE-ISOMERASE FAMILY SACCHAROMYCES-CEREVISIAE P38 MAPK REGULATES APOPTOSIS NEURONAL APOPTOSIS S-NITROSYLATION NITRIC-OXIDE HL-60 CELLS STRESS DOXORUBICIN
40
1124
1137
Cytotoxic drugs induce cell death through induction of apoptosis. This can be due to activation of a number of cell death pathways. While the downstream events in drug induced cell death are well understood, the early events are less clear. We therefore used a proteomic approach to investigate the early events in apoptosis induced by a variety of drugs in HL60 cells. Using 2D-gel electrophoresis, we were able to identify a number of protein changes that were conserved between different drug treatments. Identification of post-translational modifications (PTM) responsible for these proteome changes revealed an increase in protein oxidation in drug treated cells, as well as changes in protein phosphorylation. We demonstrate an accumulation of oxidised proteins within the ER, which lead to ER stress and calcium release and may result in the induction of apoptosis. This study demonstrates the importance of ROS mediated protein modifications in the induction of the early stages of apoptosis in response to chemotherapeutic drug treatment.
DOI 10.1080/10715760600838209
Grant Details