Zierler Susanna, Klein Barbara, Furtner Tanja, Bresgen Nikolaus, Lütz-Meindl Ursula, Kerschbaum Hubert H
Department of Cell Biology, University of Salzburg, Hellbrunnerstr. 34, 5020 Salzburg, Austria.
Brain Res. 2006 Nov 22;1121(1):12-21. doi: 10.1016/j.brainres.2006.08.122. Epub 2006 Oct 4.
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.
染色质凝聚、核体积减小以及核碎片化是许多真核细胞凋亡(程序性细胞死亡)的关键特征。在不断缩小的细胞核中染色质是如何重新分布的,这是一个有趣的问题。为了评估这个有趣的空间问题,我们以小胶质细胞系BV-2为模型,以紫外线照射作为凋亡触发因素,研究了凋亡不同阶段染色质的超微结构分布。在凋亡过程中,凝聚的染色质最初聚集在核周边,随后几乎占据整个细胞核。令人惊讶的是,细胞核并未碎片化,但凋亡细胞在细胞核以及附着于细胞核的细胞质中均显示有凝聚的染色质。在凋亡过程中,核膜扩张并通过形成大量聚集在细胞质中的电子透明小泡而在伸展程度上减小。此外,我们在BV-2细胞中观察到了众所周知的凋亡特征,如半胱天冬酶-3/7活性增加和膜联蛋白V标记,以及一系列细胞形态学改变,包括细胞皱缩、出泡和凋亡小体的形成。因此,我们的研究结果表明,紫外线诱导的染色质降解不仅限于细胞核,在BV-2细胞的细胞质中也可能发生。