English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Increasing evidence indicates that human exposure to inorganic arsenic causes cutaneous diseases and skin cancers. Nuclear factor erythroid 2-like 1 (NRF1) belongs to the cap "n" collar (CNC) basic-region leucine zipper (bZIP) transcription factor family and regulates antioxidant response element (ARE) genes. The human NRF1 gene is transcribed into multiple isoforms, which contain 584, 616, 742, 761, or 772 amino acids. We previously demonstrated that the long isoforms of NRF1 (i.e., NRF1-742, NRF1-761 and NRF1-772) are involved in the protection of human keratinocytes from acute arsenic cytotoxicity by enhancing the cellular antioxidant response. The aim of the current study was to investigate the roles of NRF1-742 and NRF1-772 in the arsenic-induced antioxidant response and cytotoxicity. We found that overexpression of NRF1-742 or NRF1-772 in human HaCaT keratinocytes decreased susceptibility to arsenic-induced apoptosis and cytotoxicity. In addition, we characterized the different protein bands observed for NRF1-742 and NRF1-772 by western blotting. The posttranslational modifications and nuclear translocation of these isoforms differed and were partially affected by arsenic exposure. Antioxidant protein levels were increased in the NRF1-742 and NRF1- 772-overexpressing cell lines. The upregulation of antioxidant protein levels was partly due to the translation of nuclear factor erythroid 2-like 2 (NRF2) and its increased nuclear transport. Overall, overexpression of NRF1-742 and NRF1-772 protected HaCaT cells from arsenic-induced cytotoxicity, mainly through translational modifications and the promotion of antioxidant gene expression.

Overexpression of NRF1-742 or NRF1-772 Reduces Arsenic-Induced Cytotoxicity and Apoptosis in Human HaCaT Keratinocytes