CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Chinese Academy of Sciences, No. 11, Beiyitiao, Zhongguancun, Beijing 100190, PR China.
Biomaterials. 2012 Jan;33(2):402-11. doi: 10.1016/j.biomaterials.2011.09.091. Epub 2011 Oct 22.
With the development of nanotechnology and the wide use of graphene, it has become necessary to assess the potential biological adverse effects of graphene. However, most of the recent publications are focused on various modified graphenes. We demonstrated biological effects of commercial pristine graphene in murine RAW 264.7 macrophages, which is an important effector cells of the innate immune system. We found that the pristine graphene can induce cytotoxicity through the depletion of the mitochondrial membrane potential (MMP) and the increase of intracellular reactive oxygen species (ROS), then trigger apoptosis by activation of the mitochondrial pathway. The MAPKs (JNK, ERK and p38) as well as the TGF-beta-related signaling pathways were found to be activated in the pristine grapheme-treated cells, which activated Bim and Bax, two pro-apoptotic member of Bcl-2 protein family. Consequently, the caspase 3 and its downstream effector proteins such as PARP were activated and the execution of apoptosis was initiated. This study provides an insight for the suppression of the apoptosis induced by the graphene through the mitochondrial pathways, the MAPKs- and TGF-beta-related signaling pathways.
随着纳米技术的发展和石墨烯的广泛应用，评估石墨烯的潜在生物不良反应变得十分必要。然而，最近的大多数出版物都集中在各种改性石墨烯上。我们在鼠源 RAW264.7 巨噬细胞中证明了商业原始石墨烯的生物学效应，巨噬细胞是先天免疫系统的重要效应细胞。我们发现原始石墨烯可以通过耗竭线粒体膜电位 (MMP) 和增加细胞内活性氧物种 (ROS) 诱导细胞毒性，然后通过线粒体途径激活引发细胞凋亡。在原始石墨烯处理的细胞中发现 MAPKs（JNK、ERK 和 p38）以及 TGF-β 相关信号通路被激活，这激活了 Bcl-2 蛋白家族中两个促凋亡成员 Bim 和 Bax。结果，caspase 3 及其下游效应蛋白如 PARP 被激活，细胞凋亡的执行被启动。这项研究为通过线粒体途径、MAPKs 和 TGF-β 相关信号通路抑制石墨烯诱导的细胞凋亡提供了新的见解。
