Zinc Supplementation, via GPR39, Upregulates PKCζ to Protect Intestinal Barrier Integrity in Caco-2 Cells Challenged by Salmonella enterica Serovar Typhimurium

The Journal of Nutrition
Yuxin ShaoBingkun Zhang

Abstract

Background: Zinc has been shown to improve intestinal barrier function against Salmonella enterica serovar Typhimurium (S. typhimurium) infection, but the mechanisms involved in this process remain undefined.Objective: We aimed to explore the roles of G protein-coupled receptor (GPR)39 and protein kinase Cζ (PKCζ) in the regulation by zinc of intestinal barrier function.Methods: A Transwell Caco-2 monolayer was pretreated with 0, 50, or 100 μM Zn and then incubated with S. typhimurium for 0-6 h. Afterward, cells silenced by the small interfering RNA for GPR39 or PKCζ were pretreated with 100 μM Zn and incubated with S. typhimurium for 3 h. Finally, transepithelial electrical resistance (TEER), permeability, tight junction (TJ) proteins, and signaling molecules GPR39 and PKCζ were measured.Results: Compared with controls, S. typhimurium decreased TEER by 62.3-96.2% at 4-6 h (P < 0.001), increased (P < 0.001) permeability at 6 h, and downregulated (P < 0.05) TJ protein zonula occludens (ZO)-1 and occludin by 104-123%, as well as Toll-like receptor 2 and PKCζ by 35.1% and 75.2%, respectively. Compared with S. typhimurium-challenged cells, 50 and 100 μM Zn improved TEER by 26.3-60.9% at 4-6 h (P < 0.001) and decreased (P < 0.001) p...Continue Reading

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Citations

Feb 2, 2018·International Journal of Molecular Sciences·Michal Hershfinkel
Jan 4, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Milena JovanovicNoam Levaot
Mar 29, 2020·Animal Science Journal = Nihon Chikusan Gakkaihō·Takuya Suzuki
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Apr 23, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yuanyang DongBingkun Zhang
Feb 13, 2021·Medical Sciences : Open Access Journal·Randal K BuddingtonScott C Howard
Mar 6, 2021·Veterinary Research·Pengpeng XiaGuoqiang Zhu
Dec 23, 2021·Cellular and Molecular Life Sciences : CMLS·Ann Katrin SauerAndreas M Grabrucker

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