Ultraviolet irradiation-induced apoptosis does not trigger nuclear fragmentation but translocation of chromatin from nucleus into cytoplasm in the microglial cell-line, BV-2

Abstract

Chromatin condensation, decrease of nuclear volume, and nuclear fragmentation are key features of apoptosis (programmed cell death) in many eukaryotic cells. How chromatin is redistributed in a continuously shrinking nucleus is an intriguing question. To evaluate this interesting spatial problem, we studied the ultrastructural distribution of chromatin in distinct stages of apoptosis using the microglial cell-line, BV-2, as a model and UV irradiation as a trigger of apoptosis. During apoptosis, condensed chromatin accumulated initially at the nuclear periphery and, subsequently, occupied almost the entire nucleus. Surprisingly, nuclei did not fragmentize, but apoptotic cells showed condensed chromatin in the nucleus as well as in the nucleus-attached cytoplasm. During apoptosis, the nuclear envelope dilated and decreased in extension by formation of numerous electron lucent vesicles, which accumulated in the cytoplasm. Furthermore, we observed in BV-2 cells well-known apoptotic features, like increased caspase-3/7 activity and annexin V labeling, as well as a sequence of cell morphological alterations, including cell shrinkage, zeiosis, and formation of apoptotic bodies. Thus, our findings suggest that UV-induced chromatin degradation is not restricted to the nucleus but may also take place in the cytoplasm in BV-2 cells.