期刊
TOXICOLOGY
卷 446, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2020.152611
关键词
Cadmium; Apoptosis; Reactive oxygen species; p53; Osteoblast
资金
- National Natural Science Foundation [31872533, 31672620, 31702304]
- National Key Research and Development Program of China [2016YFD0501208]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Project of Shandong Province Higher Educational Science and Technology Program, China [J16LF03]
Cadmium (Cd), a heavy metal produced by various industries, contaminates the environment and seriously damages the skeletal system of humans and animals. Recent studies have reported that Cd can affect the viability of cells, including osteoblasts, both in vivo and in vitro. However, the mechanism of Cd-induced apoptosis re-mains unclear. In the present study, primary rat osteoblasts were used to investigate the Cd-induced apoptotic mechanism. We found that treatment with 2 and 5 mu M Cd for 12 h decreased osteoblast viability and increased apoptosis. Furthermore, Cd increased the generation of reactive oxygen species (ROS), and, thus, DNA damage measured via p-H2AX. The level of the nuclear transcription factor p53 was significantly increased, which upregulated the expression of PUMA, Noxa, Bax, and mitochondrial cytochrome c, downregulated the expression of Bcl-2, and increased the level of cleaved caspase-3. However, pretreatment with the ROS scavenger N-acetyl-Lcysteine (NAC) or the p53 transcription specific inhibitor PFT-alpha suppressed Cd-induced apoptosis. Our results indicate that Cd can induce apoptosis in osteoblasts by increasing the generation of ROS and activating the mitochondrial p53 signaling pathway, and this mechanism requires the transcriptional activation of p53.
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