ZIP1 Is a Critical DNA Damage-Responsive Zinc Transporter Induced by Bleomycin via the TNFα-NF-κB Pathway.

Authors

Zichong Li, Jiajian Yuan, Ziqi Zhang, Hong Huang, Mei Hong

Published in

FASEB journal : official publication of the Federation of American Societies for Experimental Biology. Volume 40. Issue 16. Pages e72193. Aug 31, 2026.

Abstract

Zinc is an essential trace element that plays a significant role in DNA damage repair (DDR). Cells must maintain zinc homeostasis to effectively respond to DNA damage caused by various stressful stimuli. Members of the Zrt-, Irt-related protein (ZIP) family are recognized as key regulators of intracellular zinc levels. Dysfunction of ZIPs has been associated with numerous diseases, including cancer, cardiovascular diseases, and neurodegenerative disorders. In the present study, human bronchial epithelial BEAS-2B cells were used to investigate the response of ZIPs to bleomycin, a well-known antibiotic that induces DNA damage. Among the ZIPs that exhibited altered expression following bleomycin treatment, ZIP1 showed the most prompt and significant induction. Both knockdown and overexpression experiments demonstrated that ZIP1 plays a crucial role in the cellular response to DNA damage. Mechanistically, we found that the level of TNFα was upregulated in bleomycin-treated cells, and inhibiting this cytokine reduced the induction effect of ZIP1 caused by bleomycin. Additionally, we observed an increase in the accumulation of NF-κB in the cell nuclei, and inhibition of NF-κB also diminished the effect of bleomycin on ZIP1. Two NF-κB binding sites were identified in the upstream sequence of SLC39A1, the gene that encodes ZIP1. The application of bleomycin significantly enhanced the binding of NF-κB to these specific sites. Taken together, our study reveals that bleomycin treatment may activate the TNFα-NF-κB pathway, which in turn upregulates ZIP1, helping cells better cope with the DNA damage induced by this antibiotic.

PMID:
42599768
Bibliographic data and abstract were imported from PubMed on 15 Aug 2026.

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