Surgical Research Laboratories - Cardiac Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria.
Toxicol Lett. 2012 Aug 3;212(3):268-75. doi: 10.1016/j.toxlet.2012.05.026. Epub 2012 Jun 5.
Cadmium is a highly toxic, carcinogenic, and atherogenic element. A central principle in many Cd-induced pathophysiologies is the induction of cell death. In past studies Cd was shown to cause apoptosis, necrosis, programmed necrosis, or autophagy. This study was conducted to precisely define the end stage processes and outcome of Cd-induced cell death in endothelial cells (ECs). We show that Cd leads to acidification and permeabilization of lysosomes, followed by the release of active DNAse II from lysosomes. The absence of nuclear DNA due to DNAse II activity may have lead to misinterpretations of the type of cell death outcome in previous studies. Further, Cd-induced cell death is characterized by a massive release of lactate dehydrogenase (LDH), a gold standard marker for the occurrence of plasma membrane rupture i.e. necrosis. Importantly, lentivirus-based over-expression of the anti-apoptotic protein BCL-XL abrogates lysosomal rupture, DNA degradation and LDH release, clearly indicating that Cd induces a programmed form of cell death with a necrotic endpoint.
镉是一种毒性很强、致癌且促动脉粥样硬化的元素。许多镉诱导的病理生理学的一个中心原则是诱导细胞死亡。在过去的研究中，镉被证明可以导致细胞凋亡、坏死、程序性坏死或自噬。本研究旨在精确定义内皮细胞（ECs）中镉诱导的细胞死亡的终末过程和结果。我们表明，镉导致溶酶体酸化和通透性增加，随后溶酶体从溶酶体中释放出活性 DNAse II。由于 DNAse II 活性导致核 DNA 的缺失，可能导致以前研究中对细胞死亡结果类型的误解。此外，镉诱导的细胞死亡的特征是大量乳酸脱氢酶（LDH）的释放，LDH 是血浆膜破裂即坏死发生的金标准标志物。重要的是，基于慢病毒的抗凋亡蛋白 BCL-XL 的过表达可阻断溶酶体破裂、DNA 降解和 LDH 释放，这清楚地表明镉诱导具有坏死终点的程序性细胞死亡。
