Academic Journal
Regulation of Intestinal P-Glycoprotein by Gamma-Ray Irradiation: Impacts on Transporter Expression and Oxidative Stress.
| Τίτλος: | Regulation of Intestinal P-Glycoprotein by Gamma-Ray Irradiation: Impacts on Transporter Expression and Oxidative Stress. |
|---|---|
| Συγγραφείς: | Wu H; School of Public Health, University of South China, Hengyang 421001, China.; Academy of Military Medical Sciences, Beijing 100850, China., Yang J; Academy of Military Medical Sciences, Beijing 100850, China., Li R; Academy of Military Medical Sciences, Beijing 100850, China., Zhu W; Academy of Military Medical Sciences, Beijing 100850, China., Yuan Z; Academy of Military Medical Sciences, Beijing 100850, China., Wang M; Academy of Military Medical Sciences, Beijing 100850, China.; School of Life Sciences, Hebei University, Baoding 071002, China., Tong Y; Academy of Military Medical Sciences, Beijing 100850, China.; School of Life Sciences, Hebei University, Baoding 071002, China., Meng Z; Academy of Military Medical Sciences, Beijing 100850, China., Gu R; School of Public Health, University of South China, Hengyang 421001, China.; Academy of Military Medical Sciences, Beijing 100850, China., Sun Y; Academy of Military Medical Sciences, Beijing 100850, China., Dou G; Academy of Military Medical Sciences, Beijing 100850, China., Gan H; School of Public Health, University of South China, Hengyang 421001, China.; Academy of Military Medical Sciences, Beijing 100850, China. |
| Πηγή: | International journal of molecular sciences [Int J Mol Sci] 2026 Sep 25; Vol. 27 (19). Date of Electronic Publication: 2026 Sep 25. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI, [2000- |
| Ιατρικοί όροι (MeSH): | Gamma Rays*/adverse effects , Oxidative Stress*/radiation effects , ATP Binding Cassette Transporter, Subfamily B, Member 1*/metabolism , ATP Binding Cassette Transporter, Subfamily B, Member 1*/genetics , Intestinal Mucosa*/metabolism , Intestinal Mucosa*/radiation effects , Gene Expression Regulation*/radiation effects, Digoxin/metabolism ; Animals ; Mice ; Male ; Mice, Inbred C57BL ; Humans ; Cell Line |
| Περίληψη: | P-glycoprotein (P-gp), a key efflux drug transporter which plays a pivotal role in the in vivo pharmacokinetics of medications, undergoes alterations in expression and function following radiation exposure that can impact drug metabolism and therapeutic efficacy. Current research has found that clinical doses of radiation can affect the expression of drug transporters, while the underlying mechanisms associated with single high-dose irradiation remain to be thoroughly elucidated. This study investigates the effects of gamma-ray irradiation on the expression and transport activity of P-glycoprotein (P-gp) in various cell lines and murine small-intestinal tissues, and preliminarily explores the underlying regulatory mechanisms, thereby providing an experimental basis for research into drug transport abnormalities and interventions associated with radiation injury. Four different cell lines and male C57BL/6J mice were exposed to γ-ray irradiation from a 60Co source. P-gp gene expression was quantitatively analyzed, combined with the relative expression levels of proteins in intestinal cells and small-intestinal tissues and relevant physiological parameters. Furthermore, a Transwell intestinal epithelial cell barrier model and an in vivo mouse intestinal perfusion model were established. Using digoxin as a P-gp specific substrate, a quantitative LC-MS method was developed to assess P-gp transport activity after irradiation. Finally, transcriptome sequencing analysis of mouse small-intestinal tissue was performed, and oxidative-stress-related pathways were preliminarily detected. At the cellular level, the mRNA expression was significantly upregulated, peaking at 4.19 times that of the control group, while protein expression was also significantly upregulated, reaching a peak of approximately 2.50 times that of the control; at the animal level, the peak upregulation for mRNA and protein was 2.09-fold and 1.95-fold, respectively. Transport activity also gradually increased over time after irradiation. At the animal level, transcriptome analysis further revealed that changes in pathways such as oxidative stress and immune inflammatory responses may be jointly related to radiation-induced intestinal P-gp regulation mechanisms. Gamma-ray irradiation was associated with significant upregulation of P-gp expression and was consistent with enhanced efflux activity suggestive of P-gp involvement in various cell lines and mouse small-intestinal tissues. Radiation exposure induced intestinal damage and oxidative stress, and was associated with activation of the Nrf2/HO-1 antioxidant signaling pathway. |
| References: | J Environ Radioact. 2018 Dec;192:32-47. (PMID: 29883875) Expert Opin Drug Metab Toxicol. 2008 Jul;4(7):923-39. (PMID: 18624680) Drug Resist Updat. 2016 Jul;27:14-29. (PMID: 27449595) Drug Metab Dispos. 2025 Oct;53(10):100155. (PMID: 41072274) Mol Med Rep. 2013 Jan;7(1):187-94. (PMID: 23128850) Drug Metab Pharmacokinet. 2026 Apr;67:101528. (PMID: 41763018) J Radiat Res. 2021 Jul 10;62(4):618-625. (PMID: 33912960) Sci Rep. 2024 Jun 10;14(1):13315. (PMID: 38858439) Crit Rev Oncol Hematol. 2026 Apr;220:105168. (PMID: 41628743) Front Pharmacol. 2023 Jan 11;13:1069321. (PMID: 36712667) Disaster Med Public Health Prep. 2025 Sep 26;19:e278. (PMID: 40999667) Epigenetics. 2020 Jan - Feb;15(1-2):183-198. (PMID: 31282290) Ecotoxicol Environ Saf. 2023 Oct 1;264:115404. (PMID: 37625335) Toxicol Sci. 2025 Apr 01;204(2):181-197. (PMID: 39886939) Radiat Res. 2008 Jul;170(1):41-8. (PMID: 18582150) Pflugers Arch. 2007 Jul;454(4):587-94. (PMID: 17333245) Expert Opin Drug Discov. 2020 May;15(5):539-549. (PMID: 32154737) Adv Mater. 2025 Jul;37(26):e2415322. (PMID: 40255060) J Burn Care Res. 2020 Oct 26;:. (PMID: 33104198) J Sci Food Agric. 2025 Mar 15;105(4):2515-2526. (PMID: 39542863) Redox Biol. 2023 Oct;66:102852. (PMID: 37598463) Redox Biol. 2023 Oct;66:102857. (PMID: 37611494) Drug Resist Updat. 2026 Jan;84:101310. (PMID: 40974875) Eur J Pharmacol. 2026 Feb 15;1015:178546. (PMID: 41534556) Int J Radiat Biol. 2026;102(7):731-741. (PMID: 40758648) Drug Dev Res. 2022 Jun;83(4):825-841. (PMID: 35103340) J Clin Pharmacol. 2014 Jan;54(1):3-13. (PMID: 24166743) Cytokine Growth Factor Rev. 2024 Feb;75:1-11. (PMID: 38061920) Int J Radiat Biol. 2024;100(3):486-504. (PMID: 38166195) Int J Mol Sci. 2025 Jun 26;26(13):. (PMID: 40649901) Radiat Res. 2006 Mar;165(3):318-25. (PMID: 16494520) Amino Acids. 2005 Mar;28(2):213-9. (PMID: 15723240) Mol Cancer Res. 2008 Jan;6(1):89-98. (PMID: 18234965) Drug Metab Dispos. 2025 Jan;53(1):100022. (PMID: 39884822) Drug Metab Pharmacokinet. 2014;29(2):223-6. (PMID: 24088727) Br J Cancer. 2007 Aug 6;97(3):322-6. (PMID: 17609666) BMC Pharmacol Toxicol. 2017 May 4;18(1):20. (PMID: 28468637) Acta Pharm Sin B. 2023 Jan;13(1):227-245. (PMID: 36815051) Zhongguo Zhong Yao Za Zhi. 2017 Apr;42(8):1539-1544. (PMID: 29071859) Antioxidants (Basel). 2025 May 11;14(5):. (PMID: 40427462) Cancer Lett. 2026 Feb 28;639:218222. (PMID: 41407093) Cell Rep. 2023 Oct 31;42(10):113124. (PMID: 37733591) Somat Cell Mol Genet. 1997 Nov;23(6):391-400. (PMID: 9661702) Expert Opin Drug Metab Toxicol. 2016 Jun;12(6):633-44. (PMID: 27116192) Mol Immunol. 2018 Sep;101:471-478. (PMID: 30114619) J Radiol Prot. 2009 Jun;29(2A):A61-79. (PMID: 19454806) Cells. 2021 Apr 20;10(4):. (PMID: 33924085) Pharmaceutics. 2025 Feb 17;17(2):. (PMID: 40006635) Membranes (Basel). 2024 Oct 24;14(11):. (PMID: 39590609) Clin Transl Sci. 2026 Feb;19(2):e70487. (PMID: 41630535) Antioxidants (Basel). 2024 Feb 08;13(2):. (PMID: 38397813) Cancer Chemother Pharmacol. 2008 Jan;61(1):15-21. (PMID: 17356823) Int J Radiat Biol. 2023;99(7):1066-1079. (PMID: 36862990) Int J Mol Sci. 2025 Dec 10;26(24):. (PMID: 41465322) Neurol Res. 1999 Mar;21(2):209-15. (PMID: 10100210) Hepatology. 1994 Jul;20(1 Pt 1):170-6. (PMID: 7912687) Radiat Res. 2024 Aug 1;202(2):420-431. (PMID: 38964743) J Radiol Prot. 2019 Sep;39(3):966-977. (PMID: 30970327) Epigenetics. 2008 Sep;3(5):270-80. (PMID: 19001875) |
| Grant Information: | 7202148 Beijing Natural Science Foundation |
| Contributed Indexing: | Keywords: P-gp; gamma rays; radiation damage; transport activity |
| Substance Nomenclature: | 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1) 73K4184T59 (Digoxin) |
| Entry Date(s): | Date Created: 20261016 Date Completed: 20261016 Latest Revision: 20261020 |
| Update Code: | 20261020 |
| PubMed Central ID: | PMC13664807 |
| DOI: | 10.3390/ijms27198586 |
| PMID: | 42883831 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1422-0067 |
|---|---|
| DOI: | 10.3390/ijms27198586 |