title: Sustained JNK activation induces endothelial apoptosis: studies with colchicine and shear stress.
abstract: The disruption of microtubules by treating bovine aortic endothelial cells with 10(-7)-10(-5) M colchicine caused apoptosis, as evidenced by DNA laddering and TdT-mediated dUTP nick end labeling fluorescence staining. Colchicine treatment also induced a sustained activation of c-Jun NH(2)-terminal kinase (JNK) that lasted for >/=12 h. The blockade of JNK activity by using the negative interfering mutant JNK(K-R) markedly decreased the apoptosis induced by colchicine. Exposure of bovine aortic endothelial cells to laminar shear stress (12 dyn/cm(2)) caused a transient (<2 h) activation of JNK, and there was no induction of apoptosis. The sustained activation of JNK may play a significant role in the apoptosis induced by colchicine.
authors.affiliation: Department of Bioengineering, Whitaker Institute of Biomedical Engineering, San Diego, La Jolla, California 92093-0427, USA.
authors.forename: Y L
authors.initials: YL
authors.lastname: Hu
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.forename: J Y
authors.initials: JY
authors.lastname: Shyy
authors.forename: S
authors.initials: S
authors.lastname: Chien
mesh_terms: D000818:Animals; D001011:Aorta; D017209:Apoptosis / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000502:physiology; D013314:Stress, Mechanical; D018631:ras Proteins / Q000502:physiology
chemical_list: D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D018631:ras Proteins; D003078:Colchicine