Sustained JNK activation induces endothelial apoptosis: studies with colchicine and shear stress

The disruption of microtubules by treating bovine aortic endothelial cells with 10(-7)-10(-5) M colchicine caused apoptosis, as evidenced by DNA ladde ring and TdT-mediated dUTP nick end labeling fluorescence staining. Colchic ine treatment also induced a sustained activation of c-Jun NH2-terminal kin ase (JNK) that lasted for greater than or equal to 12 h. The blockade of JN K activity by using the negative interfering mutant JNK(K-R) markedly decre ased the apoptosis induced by colchicine. Exposure of bovine aortic endothe lial 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 c olchicine.