Biochemistry Laboratory, Central Leather Research Institute, Adyar, Chennai 600 020, India.
Toxicol In Vitro. 2010 Mar;24(2):586-96. doi: 10.1016/j.tiv.2009.10.011. Epub 2009 Oct 22.
In recent times, Cr(III)(picolinate)(3) [Cr(III)(pic)(3)] a nutritional supplement, is gaining attention because of its clastogenic and mutagenic properties. Earlier studies of ours indicated that Cr(III)(pic)(3) is cytotoxic to lymphocytes with ROS and mitochondrial events playing a role in bringing about apoptosis. Now, we report that, autoschizis is induced in lymphocytes in a concentration and time dependent manner which is confirmed through TEM and SEM. Lymphocytes treated with concentrations of 100microM of Cr(III)(pic)(3) exhibit features such as cytoplasmic bleb, self excision of cytoplasm, cytoplasmic leakage and membrane bound bodies formed from the excised pieces apart from apoptosis and necrosis. Though autoschizis has been described in tumor cell lines treated with menadione and ascorbate, occurrence of this cell death in normal T-lymphocytes is reported here. The cellular events that accompany autoschizis are found to be increase in intracellular Reactive Oxygen Species (ROS) and cytoplasmic lactate dehydrogenase, loss of mitochondrial membrane potential (MMP) and depletion of ATP. Further, autoschizis is effected through increases in DNase I and DNase II activity with a concomitant decrease in caspase-3 activity which leads to a random cleavage of the DNA as demonstrated by a smear like pattern after electrophoresis on agarose gel.
近年来，作为一种营养补充剂的 Cr(III)(吡啶甲酸根)(3)[Cr(III)(pic)(3)]因其致突变和致裂作用而受到关注。我们之前的研究表明，Cr(III)(pic)(3)对淋巴细胞具有细胞毒性，活性氧(ROS)和线粒体事件在诱导细胞凋亡中起作用。现在，我们报告说，Cr(III)(pic)(3)以浓度和时间依赖的方式诱导淋巴细胞发生自噬，这通过 TEM 和 SEM 得到证实。用 100μM 的 Cr(III)(pic)(3)处理的淋巴细胞表现出细胞质泡、细胞质自我切除、细胞质渗漏和由切除的碎片形成的膜结合体等特征，除了凋亡和坏死之外。尽管自噬已在接受甲萘醌和抗坏血酸处理的肿瘤细胞系中被描述，但这里报道了正常 T 淋巴细胞中发生这种细胞死亡的情况。伴随自噬发生的细胞事件被发现是细胞内活性氧(ROS)和细胞质乳酸脱氢酶增加，线粒体膜电位(MMP)丧失和 ATP 耗竭。此外，自噬是通过增加 DNA 内切酶 I 和 DNA 内切酶 II 的活性以及同时降低 caspase-3 的活性来实现的，这导致 DNA 的随机切割，如琼脂糖凝胶电泳后的弥散模式所示。
