Inhibition of ICE-family cysteine proteases rescues murine lymphocytes from lipoxygenase inhibitor-induced apoptosis.
Two lipophilic derivatives of caffeic acid which inhibit lipoxygenase, caffeic acid phenethyl ester (CAPE) and N,N'-dicyclohexyl-O-(3,4-dihydroxycinnamoyl)-isourea (DCHCU), reduced the proliferative response of murine splenocytes to concanavalin A in vitro. Both CAPE and DCHCU induced apoptosis in murine thymocyte cultures as verified by flow cytometry and by visualisation of DNA with acridine orange staining. CAPE-induced apoptosis was inhibited by z-VAD-fmk, an inhibitor of the interleukin-1beta-converting enzyme family of cysteine proteases. We suggest that the lipoxygenase pathway of arachidonic acid metabolism plays a role in regulating lymphocyte responses such as proliferation and apoptosis.
A.N. Belozerzky Institute of Physico-Chemical Biology, Moscow State University, Russian Federation. mirzoeva@bk408.genebee.msu.su
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D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002109:Caffeic Acids / Q000494:pharmacology; D020170:Caspase 1; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000494:pharmacology; D011429:Propolis / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
D000590:Amino Acid Chloromethyl Ketones; D002109:Caffeic Acids; D015853:Cysteine Proteinase Inhibitors; D016859:Lipoxygenase Inhibitors; C093481:N,N'-dicyclohexyl-O-(3,4-dihydroxycinnamoyl)isourea; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D003208:Concanavalin A; D014508:Urea; D011429:Propolis; D011794:Quercetin; D003546:Cysteine Endopeptidases; D020170:Caspase 1; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol