LPS-induced signals in activation of caspase-3-like protease, a key enzyme regulating apoptotic cell damage into a macrophage-like cell line, J774.1, in the presence of cycloheximide.
The earliest observed apoptotic change in a macrophage-like cell line, J774.1, treated with lipopolysaccharide (LPS) in the presence of cycloheximide (CHX) was a selective increase in caspase-3-like activity. The addition of polymyxin B, TPCK, herbimycin A, or genistein, all of which inhibited LPS-induced tumor necrosis factor alpha (TNF-alpha) production by macrophages, suppressed the activation of the caspase-3-like protease in these macrophages treated simultaneously with CHX. However, SB202190 and SB203580, inhibitors of MAP kinase, and PD98059, an inhibitor of MAP-kinase kinase (MEK), showed no effect on the activation of the caspase-3-like protease or on the cell damage of the macrophages treated with LPS and CHX, whereas they inhibited LPS-induced TNF-alpha production. These results suggest that some of the early signals in LPS-treated macrophages are common to the subsequent pathways for TNF-alpha production and caspase-3-like protease activation, but the later signals, like MAP-kinase kinase or MAP-kinase, are not involved in the pathways for caspase-3-like protease activation.
Karahashi
H
H
Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Tokyo, Japan.
Amano
F
F
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D003513:Cycloheximide / Q000378:metabolism* / Q000494:pharmacology; D004789:Enzyme Activation; D008070:Lipopolysaccharides / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008934:Mitogens / Q000378:metabolism* / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction
D008070:Lipopolysaccharides; D008934:Mitogens; D011500:Protein Synthesis Inhibitors; D003513:Cycloheximide; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases