Program of Environmental Toxicology, School of Public Health, China Medical University, Shenyang, Liaoning, China.
Department of Histology and Embryology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China.
Oxid Med Cell Longev. 2017;2017:7417694. doi: 10.1155/2017/7417694. Epub 2017 Sep 10.
Arsenic is a well-known human carcinogen. Stem cells are indicated to be involved in arsenic carcinogenesis and have a survival selection advantage during arsenic exposure with underlying mechanisms undefined. In the present study, we demonstrated that CD34-enriched cells derived from HaCaT human keratinocytes showed stem-like phenotypes. These cells were more resistant to arsenic toxicity and had higher arsenic efflux ability than their mature compartments. The master transcription factor in antioxidant defense, nuclear factor erythroid 2-related factor 2 (NRF2) with its downstream genes, was highly expressed in CD34-enriched cells. Stable knockdown of abolished the hyperresistance to arsenic toxicity and holoclone-forming ability of CD34-enriched cells. Our results suggest that skin epithelial stem/progenitor cells are more resistant to arsenic toxicity than mature cells, which is associated with the high innate expression of in skin epithelial stem/progenitor cells.
砷是一种众所周知的人类致癌物。研究表明，干细胞参与砷致癌作用，并在砷暴露期间具有生存选择优势，但潜在机制尚不清楚。本研究表明，从 HaCaT 人角质形成细胞中富集的 CD34 细胞表现出干细胞样表型。这些细胞对砷毒性的抵抗力更强，砷外排能力也高于其成熟细胞。抗氧化防御的主要转录因子，红细胞生成 2 相关因子 2（NRF2）及其下游基因，在 CD34 细胞中高表达。稳定敲低 可消除 CD34 细胞对砷毒性的超抗性和克隆形成能力。我们的研究结果表明，皮肤上皮干细胞/祖细胞比成熟细胞对砷毒性的抵抗力更强，这与皮肤上皮干细胞/祖细胞中 高表达有关。
