Inactivation of cellular caspases by peptide-derived tryptophan and tyrosine peroxides.
Peroxides generated on peptides and proteins within cells, as a result of radical attack or reaction with singlet oxygen, are longer-lived than H(2)O(2) due to their poor removal by protective enzymes. These peroxides readily oxidize cysteine residues and can inactivate thiol-dependent enzymes. We show here that Trp- and Tyr-derived peptide peroxides, generated by singlet oxygen, inhibit caspase activity in the lysates of apoptotic Jurkat cells. N-Ac-Trp-OMe peroxide was the most effective inhibitor, and was 30-fold more effective than H(2)O(2) under identical conditions. As such, protein peroxides could modulate the progression of apoptosis in cells in which they are generated.
Hampton
Mark B
MB
Free Radical Research Group, Department of Pathology, Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand.
Morgan
Philip E
PE
Davies
Michael J
MJ
D000596:Amino Acids / Q000494:pharmacology; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D019169:Jurkat Cells; D010545:Peroxides / Q000378:metabolism / Q000494:pharmacology*; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000596:Amino Acids; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C467059:N-acetyltryptophan methyl ester peroxide; D010545:Peroxides; C467058:tryptophan peroxide; C104002:tyrosine peroxide; D014443:Tyrosine; D014364:Tryptophan; D006861:Hydrogen Peroxide