The extracellular release of HMGB1 during apoptotic cell death
The extracellular release of HMGB1 during apoptotic cell death
复制标题
DOI：
10.1152/ajpcell.00616.2005
复制
发表时间：
2006-12-01
影响因子：
5.5
通讯作者：
Pisetsky, David S.
中科院分区：
文献类型：
--
作者：
Bell, Charles W.;Jiang, Weiwen;Pisetsky, David S.
高迁移率族蛋白1(HMGB1)是一种具有双重功能的非组蛋白核蛋白。在细胞内，HMGB1结合DNA并调节转录，而在细胞外，它作为一种细胞因子，介导内毒素的晚期效应。HMGB1在内毒素刺激的巨噬细胞和正在发生坏死但不发生凋亡的细胞中被证明移动到细胞外空间。HMGB1在死亡过程中的差异释放可以反映这些环境中染色质的结构以及HMGB1易位的机制。由于凋亡细胞可以释放一些核分子，如HMGB1可以与之结合的DNA，因此我们研究了HMGB1在凋亡和坏死过程中是否也会释放。为此，用化学诱导剂(星形孢子素、依托泊苷或喜树碱)处理Jurkat细胞，用Western blotting检测HMGB1释放到培养液中的情况。这些实验结果表明，HMGB1以时间依赖的方式出现在凋亡的Jurkat细胞的培养液中，Z-VAD-fmk可以减少这种释放。经这些药物处理的PANC-1和U937细胞表现出相似的释放。此外，诱导凋亡的HeLa细胞表现出HMGB1的释放。此外，我们使用共聚焦显微镜显示，HMGB1和DNA在Jurkat细胞凋亡过程中改变了它们的核位置。总之，这些研究表明，HMGB1的释放可以发生在细胞凋亡和坏死的过程中，并表明释放过程可能随着细胞类型的不同而不同。
High mobility group box 1 protein (HMGB1) is a non-histone nuclear protein with dual function. Inside the cell, HMGB1 binds DNA and regulates transcription, whereas outside the cell, it serves as a cytokine and mediates the late effects of LPS. The movement of HMGB1 into the extracellular space has been demonstrated for macrophages stimulated with LPS as well as cells undergoing necrosis but not apoptosis. The differential release of HMGB1 during death processes could reflect the structure of chromatin in these settings as well as the mechanisms for HMGB1 translocation. Since apoptotic cells can release some nuclear molecules such as DNA to which HMGB1 can bind, we therefore investigated whether HMGB1 release can occur during apoptosis as well as necrosis. For this purpose, Jurkat cells were treated with chemical inducers of apoptosis (staurosporine, etoposide, or camptothecin), and HMGB1 release into the medium was assessed by Western blotting. Results of these experiments indicate that HMGB1 appears in the media of apoptotic Jurkat cells in a time-dependent manner and that this release can be reduced by Z-VAD-fmk. Panc-1 and U937 cells treated with these agents showed similar release. In addition, HeLa cells induced to undergo apoptosis showed HMGB1 release. Furthermore, we showed using confocal microscopy that HMGB1 and DNA change their nuclear location in Jurkat cells undergoing apoptosis. Together, these studies indicate that HMGB1 release can occur during the course of apoptosis as well as necrosis and suggest that the release process may vary with cell type.