ROS and protein oxidation in early stages of cytotoxic drug induced apoptosis.
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.
England
Karen
K
Department of Biochemistry, Biosciences Institute, University College Cork, Cork, Ireland.
Driscoll
Carolyn O
CO
Cotter
Thomas G
TG
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002469:Cell Separation; D015180:Electrophoresis, Gel, Two-Dimensional; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D017382:Reactive Oxygen Species; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000970:Antineoplastic Agents; D011506:Proteins; D017382:Reactive Oxygen Species; D020169:Caspases