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Zinc Modulates the Response to Apoptosis in an In Vitro Model with High Glucose and Inflammatory Stimuli in C2C12 Cells

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Abstract

Apoptosis is programmed cell death and its alteration is related to cancer, neurologic, autoimmune, and chronic diseases. A number of factors can affect this process. The aim of this paper is to study the effect of supplemental zinc on apoptosis-related genes in C2C12 myoblast cells after being challenged with a series of stimuli, such as high glucose, insulin, and an inflammatory agent. C2C12 myoblast cells were cultured for 24 h with zinc (Zn) (ZnSO4) 10 or 100 μM and/or glucose 10 or 30 mM. In addition to these stimuli, the cells were challenged with insulin 1 nM or interleukin-6 (IL-6) 5 nM. The mRNA expression of proapoptotic genes caspase 3 and Fas, the antiapoptotic genes, Xiap and Bcl-xL and the ratio of pro-/antiapoptotic genes Bax/Bcl-2, were determined by qRT-PCR. The expression of caspase-3 gene was significantly increased in the presence of the combination high Zn/high glucose with and without the presence of insulin and IL6 in the culture medium Fas expression instead, showed uneven responses. The expression of Bcl-xL and Xiap was increased in most conditions by having high Zn in the medium regardless of the presence of insulin or IL6. Bax/Bcl2 ratio was decreased in the presence of high Zn. Zn was able to stimulate the expression of antiapoptotic genes. This effect was specially noted in high-glucose conditions with and without the presence of insulin. This effect is partially overridden by the presence of an inflammatory agent such as IL-6.

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Abbreviations

DMT1:

Divalent metal transporter 1

ZnT:

Zinc transporter

FBS:

Fetal bovine serum

qRT-PCR:

Quantitative reverse transcription–polymerase chain reaction

B2M:

Beta-2 microglobulin

ANOVA:

Analysis of variance

SEM:

Standard error of the mean

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Funding

This research was funded by the National Fund for Development of Science and Technology (FONDECYT), research project 1120323.

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Authors and Affiliations

  1. Micronutrient Laboratory, Institute of Nutrition and Food Technology, University of Chile, El Líbano 5524, Macul, Santiago, Chile

    Mónica Andrews-Guzmán & Miguel Arredondo-Olguín

  2. Department of Nutrition, Faculty of Medicine, University of Chile, Avenida Independencia 1027, Independencia, Santiago, Chile

    Manuel Ruz

Authors
  1. Mónica Andrews-Guzmán
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  2. Manuel Ruz
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  3. Miguel Arredondo-Olguín
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Contributions

MAG, MR, and MAO conception and design of research. MAG performed experiments. MAG and MAO analyzed data. MAG, MR, and MAO interpreted results of experiments. MAG and MAO prepared figures. MAG drafted manuscript. MAG, MR, and MAO edited and revised manuscript. MAO and MR approved final version of the manuscript.

Corresponding author

Correspondence to Miguel Arredondo-Olguín.

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Conflicts of Interest

Manuel Ruz and Miguel Arredondo received payment from the research project FONDECYT 1120323. The rest of authors declare that they have no conflicts of interest.

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Andrews-Guzmán, M., Ruz, M. & Arredondo-Olguín, M. Zinc Modulates the Response to Apoptosis in an In Vitro Model with High Glucose and Inflammatory Stimuli in C2C12 Cells. Biol Trace Elem Res 199, 2288–2294 (2021). https://doi.org/10.1007/s12011-020-02348-9

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  • DOI: https://doi.org/10.1007/s12011-020-02348-9

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