Academic Journal
The heavy ion-induced up-regulation of ZIP14 is mediated by the PKCNrf2 pathway.
| Τίτλος: | The heavy ion-induced up-regulation of ZIP14 is mediated by the PKCNrf2 pathway. |
|---|---|
| Συγγραφείς: | Zhang Z; Guangdong Laboratory for Lingnan Modern Agriculture, College of Life Sciences, South China Agricultural University, Guangzhou, China; Guangdong Provincial Key Laboratory for the Development Biology and Environmental Adaptation of Agricultural Organisms, South China Agricultural University, Guangzhou, China., Yuan J; Guangdong Laboratory for Lingnan Modern Agriculture, College of Life Sciences, South China Agricultural University, Guangzhou, China; Guangdong Provincial Key Laboratory for the Development Biology and Environmental Adaptation of Agricultural Organisms, South China Agricultural University, Guangzhou, China., Hong M; Guangdong Laboratory for Lingnan Modern Agriculture, College of Life Sciences, South China Agricultural University, Guangzhou, China; Guangdong Provincial Key Laboratory for the Development Biology and Environmental Adaptation of Agricultural Organisms, South China Agricultural University, Guangzhou, China. Electronic address: mh2788@scau.edu.cn. |
| Πηγή: | Life sciences in space research [Life Sci Space Res (Amst)] 2026 Sep; Vol. 52, pp. 185-195. Date of Electronic Publication: 2026 Mar 05. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Ltd Country of Publication: Netherlands NLM ID: 101632373 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2214-5532 (Electronic) Linking ISSN: 22145524 NLM ISO Abbreviation: Life Sci Space Res (Amst) Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Amsterdam : Elsevier Ltd, [2014]- |
| Ιατρικοί όροι (MeSH): | Up-Regulation*/radiation effects , Cation Transport Proteins*/metabolism , Cation Transport Proteins*/genetics , Protein Kinase C*/metabolism , Heavy Ions*/adverse effects, Zinc/metabolism ; Signal Transduction/radiation effects ; DNA Repair/radiation effects ; Epithelial Cells/radiation effects ; Epithelial Cells/metabolism ; Humans ; DNA Damage ; Cell Line ; NF-E2-Related Factor 2 |
| Περίληψη: | Heavy ion irradiation (IR) creates complex DNA lesions, posing a significant biological risk during space exposure. Zinc, an essential trace element, plays a crucial role in DNA repair; however, the mechanisms that maintain zinc homeostasis following irradiation are not well understood. In the present study, human bronchial epithelial BEAS-2B cells irradiated with carbon ions and cultured under zinc-deficient conditions exhibited increased and persistent γ-H2AX foci when compared to cells grown in medium with normal zinc contents. Further investigation revealed that ZIP14, a member of the Zrt/Irt-like protein (ZIP) family, is involved in the cellular response to IR-induced DNA damage repair (DDR). The knockdown of ZIP14 significantly reduced the cells' capacity for DDR. Additionally, protein kinase C (PKC), which is known to be activated by radiation, was found to play a role in regulating ZIP14. Overexpressing or activating PKC enhanced ZIP14 expression, while silencing PKC significantly attenuated the induction of ZIP14 by IR. PKC likely affects ZIP14 through its phosphorylation of Nrf2, which facilitates the nuclear translocation and accumulation of the transcription factor. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) analyses identified a binding site (-2221 bp to -2210 bp) for Nrf2 in the upstream regulatory region of SLC39A14, the gene encoding ZIP14. In conclusion, our results demonstrate that ZIP14, regulated by the PKCNrf2 pathway, plays an important role in adjusting zinc homeostasis in response to DNA damage caused by heavy ion IR. (Copyright © 2026 Committee on Space Research (COSPAR). Published by Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Heavy ion irradiation; Nrf2; PKC; ZIP14; Zinc homeostasis |
| Substance Nomenclature: | 0 (Cation Transport Proteins) EC 2.7.11.13 (Protein Kinase C) J41CSQ7QDS (Zinc) 0 (NFE2L2 protein, human) 0 (NF-E2-Related Factor 2) |
| Entry Date(s): | Date Created: 20260814 Date Completed: 20260814 Latest Revision: 20260814 |
| Update Code: | 20260815 |
| DOI: | 10.1016/j.lssr.2026.03.001 |
| PMID: | 42601150 |
| Βάση Δεδομένων: | MEDLINE |
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