ZIP1 Is a Critical DNA Damage-Responsive Zinc Transporter Induced by Bleomycin via the TNFα-NF-κB Pathway
Zichong Li1, Jiajian Yuan1, Ziqi Zhang1,2
1Guangdong Laboratory for Lingnan Modern Agriculture, College of Life Sciences, South China Agricultural University, Guangzhou, China.
Summary
Zinc transporter ZIP1 is crucial for cellular response to DNA damage. Bleomycin treatment upregulates ZIP1 via the TNFα-NF-κB pathway, enhancing DNA repair mechanisms.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Zinc is vital for DNA damage repair (DDR).
- ZIP family proteins regulate intracellular zinc levels, impacting disease.
- ZIP dysfunction is linked to cancer, cardiovascular, and neurodegenerative diseases.
Purpose of the Study:
- Investigate ZIP protein response to DNA damage induced by bleomycin.
- Elucidate the role of ZIP1 in cellular DNA damage response.
- Determine the molecular mechanisms underlying ZIP1 regulation by bleomycin.
Main Methods:
- Used human bronchial epithelial BEAS-2B cells.
- Treated cells with bleomycin, a DNA-damaging antibiotic.
- Performed ZIP gene expression analysis, knockdown, and overexpression studies.
- Investigated the roles of TNFα and NF-κB signaling pathways.
- Analyzed NF-κB binding to the SLC39A1 gene promoter.
Main Results:
- Bleomycin treatment significantly induced ZIP1 expression in BEAS-2B cells.
- ZIP1 knockdown impaired cellular response to DNA damage, while overexpression enhanced it.
- Bleomycin upregulated TNFα, and its inhibition reduced ZIP1 induction.
- NF-κB activation and nuclear accumulation were observed; NF-κB inhibition diminished ZIP1 induction.
- NF-κB binding to identified sites in the SLC39A1 promoter was enhanced by bleomycin.
Conclusions:
- Bleomycin-induced DNA damage activates the TNFα-NF-κB pathway.
- This pathway upregulates ZIP1 expression.
- Upregulated ZIP1 contributes to cellular defense against bleomycin-induced DNA damage.
- ZIP1 plays a critical role in cellular adaptation to genotoxic stress.
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