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Effects of cadmium on osteoblast cell line: Exportin 1 accumulation, p-JNK activation, DNA damage and cell apoptosis(Open Access)

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机构: [a]Jinan University, Guangzhou, China [b]Department of traditional Chinese medicine, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China [c]The second Clinical Medical College of Jinan University, Shenzhen, Guangdong, China
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关键词: Apoptosis Cadmium Caspase Exportin 1 JNK MC3T3-E1

摘要:
Cadmium is an environmental metal pollutant that has been a focus of research in recent years, which is reported to cause bone disease; however, its skeletal toxicity and the mechanism involved are not yet fully known. Therefore, this study used MC3T3-E1 subclone 14 cells to determine the mechanism of cadmium toxicity on bone. Cadmium chloride (Cd) significantly reduced cell viability in a concentration-dependent manner. Exposure to Cd inhibited osteoblast-related proteins (Runx2, Col-1, STC2) and decreased alkaline phosphatase (ALP) activity. Cd caused Exportin-1 accumulation and induced DNA damage. Cd significantly down-regulated caspase 9 and induced cleaved-PARP, cleaved-caspase 3 protein level. Treatment with JNK inhibitor, SP600125, suppressed cadmium-induced elevation in the ratio of phosphorylation of JNK to JNK. Inhibition of caspase with pan-caspase inhibitor, Z-VAD-FMK, prevented MC3T3-E1 subclone 14 cells from cadmium-induced reduction of Runx2, STC2, caspase 9, and accumulation of cleaved PARP and cleaved caspase 3. Cd-induced cell survival enhanced by SP600125 but rescued by Z-VAD-FMK or KPT-335. These results suggest that cadmium cytotoxicity on bone involved exportin 1 accumulation, phosphorylation of JNK, induction of DNA damage and pro-apoptosis, which was induced by activation of caspase-dependent pathways. © 2020 The Authors

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出版当年[2020]版:
大类 | 2 区 环境科学与生态学
小类 | 2 区 环境科学 2 区 毒理学
最新[2025]版:
大类 | 2 区 环境科学与生态学
小类 | 1 区 毒理学 2 区 环境科学
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出版当年[2019]版:
Q1 TOXICOLOGY Q1 ENVIRONMENTAL SCIENCES
最新[2023]版:
Q1 ENVIRONMENTAL SCIENCES Q1 TOXICOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

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第一作者机构: [a]Jinan University, Guangzhou, China [b]Department of traditional Chinese medicine, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China [c]The second Clinical Medical College of Jinan University, Shenzhen, Guangdong, China
通讯作者:
通讯机构: [a]Jinan University, Guangzhou, China [b]Department of traditional Chinese medicine, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China [*1]Jinan University, Guangzhou, China.
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