NRF2 Is a Potential Modulator of Hyperresistance to Arsenic Toxicity in Stem-Like Keratinocytes.
Xiafang WuBei YangYuxin HuRu SunHuihui WangJingqi FuYongyong HouJingbo PiYuanyuan XuPublished in: Oxidative medicine and cellular longevity (2017)
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 CD34high-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 CD34high-enriched cells. Stable knockdown of NRF2 abolished the hyperresistance to arsenic toxicity and holoclone-forming ability of CD34high-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 NRF2 in skin epithelial stem/progenitor cells.
Keyphrases
- induced apoptosis
- oxidative stress
- drinking water
- cell cycle arrest
- stem cells
- heavy metals
- endoplasmic reticulum stress
- nuclear factor
- endothelial cells
- gene expression
- cell death
- risk assessment
- signaling pathway
- soft tissue
- wound healing
- bone marrow
- genome wide
- induced pluripotent stem cells
- anti inflammatory
- dna binding