Myosin heavy chain degradation during apoptosis in endothelial cells.
The cytoskeleton undergoes dramatic changes during apoptosis and many cytoskeletal proteins are known to be degraded during this process. The number of proteases found to be involved in apoptosis is growing but the role of the proteolysis they cause remains poorly understood. This report describes for the first time that myosin heavy chain is cleaved in aortic endothelial cell apoptosis induced either by tumour necrosis factor-alpha or okadaic acid. The cleavage was specific since a well-defined major 97 kDa fragment of myosin heavy chain was produced. The intermediate filament component vimentin was also cleaved into well-defined fragments (31, 28 and 23 kDa). Kinetic studies showed that proteolysis occurred concomitantly with the morphological changes associated with apoptosis, i.e. cellular condensation and fragmentation in apoptotic bodies. These data suggest that the degradation of myosin and vimentin could be involved in the execution of the morphological alterations observed during apoptotic cell death.
Suarez-Huerta
N
N
Institut de Recherche Interdisciplinaire en Biologie Humaine et Nucléaire, Faculté de Médecine, Free University of Brussels, Belgium. nsuarez@ulb.ac.be
Lecocq
R
R
Mosselmans
R
R
Galand
P
P
Dumont
J E
JE
Robaye
B
B
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000166:cytology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D002417:Cattle; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D015180:Electrophoresis, Gel, Two-Dimensional; D004730:Endothelium, Vascular / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D008970:Molecular Weight; D018995:Myosin Heavy Chains / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D019319:Okadaic Acid / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014746:Vimentin / Q000032:analysis / Q000737:chemistry
D000590:Amino Acid Chloromethyl Ketones; D015853:Cysteine Proteinase Inhibitors; D004791:Enzyme Inhibitors; D011500:Protein Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; D014746:Vimentin; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D019319:Okadaic Acid; D003513:Cycloheximide; D018995:Myosin Heavy Chains