Jana Mahadevan, Rajaram Anantanarayanan, Rajaram Rama
Biochemistry Laboratory, Central Leather Research Institute, Adyar, Chennai 600 020, India.
Toxicol Appl Pharmacol. 2009 Jun 15;237(3):331-44. doi: 10.1016/j.taap.2009.04.006. Epub 2009 Apr 16.
Cr(III)(picolinate)(3) [Cr(III)(pic)(3)] is currently used as a nutritional supplement and for treating Type-2 diabetes. The effect of Cr(III)(pic)(3) uptake in peripheral blood lymphocytes is investigated in this study. From the cytotoxicity data, DNA fragmentation pattern, Annexin V staining, TUNEL positivity and the ultrastructural characteristics such as chromatin condensation and formation of apoptotic bodies, it is clear that Cr(III)(pic)(3) induces a concentration dependent apoptosis. It is shown that reactive oxygen species (ROS) produced by treatment with Cr(III)(pic)(3) leads to apoptosis, since we find that pretreatment with N-acetyl cysteine inhibits the process. Using Western blotting technique and fluorescence measurements, the downstream signaling molecules have also been identified. Cr(III)(pic)(3) treatment leads to collapse of the mitochondrial membrane potential, Bax expression, increase in cytosolic cytochrome c content and active caspase-3 and DNA fragmentation and all these manifestations are reduced by pretreating the lymphocytes with N-acetyl cysteine. Thus, it is shown that Cr(III)(pic)(3) is cytotoxic to lymphocytes with ROS and mitochondrial events playing a role in bringing about apoptosis.
三（吡啶甲酸）铬（III）[Cr(III)(pic)(3)]目前用作营养补充剂并用于治疗2型糖尿病。本研究调查了Cr(III)(pic)(3)在外周血淋巴细胞中的摄取效果。从细胞毒性数据、DNA片段化模式、膜联蛋白V染色、TUNEL阳性以及诸如染色质浓缩和凋亡小体形成等超微结构特征来看，很明显Cr(III)(pic)(3)诱导浓度依赖性凋亡。研究表明，用Cr(III)(pic)(3)处理产生的活性氧（ROS）导致凋亡，因为我们发现用N-乙酰半胱氨酸预处理可抑制该过程。使用蛋白质免疫印迹技术和荧光测量，还鉴定了下游信号分子。Cr(III)(pic)(3)处理导致线粒体膜电位崩溃、Bax表达、细胞溶质细胞色素c含量增加以及活性caspase-3和DNA片段化，而用N-乙酰半胱氨酸预处理淋巴细胞可减少所有这些表现。因此，研究表明Cr(III)(pic)(3)对淋巴细胞具有细胞毒性，ROS和线粒体事件在导致凋亡中起作用。
