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Session: Micronutrients, Supplements and Chronic Disease Mechanisms (Poster Theater Flash Session 12)

(PTFS12-06-23) Investigation of Cellular Zinc Influx in In Vitro Senescent Enterocyte Models

Tuesday, July 25, 2023
10:25 AM – 10:29 AM ET
Location:  Fairfax

    Presenting Author(s)

  • KT

    Kristofer Terrell, BS (he/him/his)

    Graduate Student
    University of Connecticut
    Mansfield Center, Connecticut, United States

    Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

    • Co-Author(s)

  • SC

    Sangyong Choi, Ph.D.

    University of Connecticut

Disclosure(s):
Kristofer Terrell, BS: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: The classical physiology of aging comes with many hallmarks, including cellular senescence and dysregulated nutrient signaling. Studies have found differences in zinc (Zn) concentration in various tissues and fluids in young versus aged mice and humans. In this study, we aimed to investigate cellular senescence’s effects on the transcriptional regulation of the two main Zn transporter families: SLC39A1-14 (ZIPs) and SLC30A1-10 (ZnTs), and the effects of senescence on cellular Zn concentrations.

Methods: We employed two methods of inducing senescence into C2BBe1 cells, low dose etoposide administration and gamma irradiation. Regarding the etoposide method, cells were seeded, and media was replaced 24 hrs later with 5 µM etoposide or equal volumes dimethyl sulfoxide as negative control. After 48 hrs, cells were allowed to recover in growth media for 24 hrs until analyzed. For gamma irradiation, cells were seeded, then 24 hrs later exposed to 5 grays (Cesium-137) and allowed 48 hrs to recover before analysis. Zn treatment was 2 hrs of 200 µM zinc sulfate, followed by either Zn measurement via colorimetric assay or extraction of total RNA. Following RNA extraction, RT-qPCR was done on the ZIP and ZnT family genes which have high expression based on publicly available RNA-seq data.

Results: CDKN1A mRNA expression increased approximately 4-fold in both etoposide and irradiation models, indicating senescence. Basal cellular Zn levels were not changed via induction of senescence in both models. Zn transporter genes encoding ZIP 1, 2, 3, 6, 7, 9, 10, 14 and ZnT 1, 5, 6, 9 were stably expressed upon induction of senescence. In etoposide-treated cells, we found that the basal SLC30A7 expression increased and that SLC39A1 and SLC39A14 increased upon Zn administration, which was not shown in control cells. However, these effects were not seen in the irradiation models.

Conclusions: In two cellular senescence models of enterocytes, intracellular zinc and zinc uptake efficiency were not altered compared to non-senescent cells. Results indicate that enterocyte senescence may not cause inefficient zinc absorbance in aged intestines, suggesting instead that other age-related factors contribute to the dysregulation of zinc homeostasis.

Funding Sources: University of Connecticut