Cytoskeletal changes in non-apoptotic cell death.

Abstract

Dynamic morphology and cytoskeletal changes in Hep-2 cells exhibiting features of non-apoptotic cell death after treatment with zinc were studied using immunofluorescence microscopy and spectrofluorimetry. Among early morphological changes in treated cells was development of vacuolization, surface blebbing, relatively rapid cell detachment from substratum, cell shrinkage and, in some cases, appearance of membrane protrusions. Staining of microfilaments revealed rapid rearrangement and subsequent loss of F-actin accompanied by changes in the amount and localization of G-actin. The use of specific kinase and caspase inhibitors did not prevent surface blebbing as well as other morphological features in dying cells. Dying cells were only weakly positive for phosphatidyl serine and showed only a transient activation of caspase-9 with no signs of activation of caspase-3. These results suggest the existence of nonapoptotic cell death showing morphological features of both apoptosis and necrosis but, biochemically, resembling some other type of cell death.