The triggering of apoptosis in macrophages by pristine graphene through the MAPK and TGF-beta signaling pathways.
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.
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.
Yang
Y
Li
Ying
Y
Liu
Yujian
Y
Fu
Taotao
T
Wei
Laurent
L
Le Guyader
Ge
G
Gao
Ru-Shi
RS
Liu
Yan-Zhong
YZ
Chang
Chunying
C
Chen
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3; D002460:Cell Line; D006108:Graphite / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000235:genetics*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D051028:bcl-2-Associated X Protein; D006108:Graphite; C505409:Casp3 protein, mouse; D053148:Caspase 3