Protease Inhibitors Cause Necrotic Cell Death in Chlamydomonas reinhardtii by Inducing the Generation of Reactive Oxygen Species.
Protease inhibitors affecting the activity of the proteasome were reported to induce programmed cell death (apoptosis) in some mammalian cell lines. Proteasome activity can be suppressed by specific peptide derivatives and by N-tosyl-lysine-chloromethyl-ketone (TLCK) and N-tosyl-phenylalanine-chloromethyl-ketone (TPCK), which affect the trypsine- and chymotrypsine-like activities of the proteasome, respectively. Particularly TLCK and TPCK caused necrotic cell death in the unicellular green alga Chlamydomonas reinhardtii. As a control, the effects of these protease inhibitors on the survival of human WISH cells were also studied. Bleaching of the Chlamydomonas cells after addition of TLCK or TPCK indicated that reactive oxygen species (ROS) were involved in this process. Indeed, increased levels of ROS were detected in Chlamydomonas cells treated with TLCK or TPCK. Furthermore, cell death induced by these protease inhibitors was accelerated by illumination and prevented or slowed down by scavengers of ROS.
Institute for Biochemistry, Charité, Charité-Platz 1/Virchowweg 6, D-10117 Berlin, Germany.|Institute of Microbiology, Friedrich-Schiller-University, Neugasse 24, D-07743 Jena, Germany.
Juergen
J
Voigt
Institute of Microbiology, Friedrich-Schiller-University, Neugasse 24, D-07743 Jena, Germany.
Johannes
J
Woestemeyer
D000590:Amino Acid Chloromethyl Ketones / Q000378:metabolism; D000650:Amnion / Q000166:cytology; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D016825:Chlamydomonas reinhardtii / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*
D000590:Amino Acid Chloromethyl Ketones; D017382:Reactive Oxygen Species; D015842:Serine Proteinase Inhibitors; D046988:Proteasome Endopeptidase Complex
Apoptosis; necrosis