Cell‑specific and roasting‑dependent regulation of the Keap1/Nrf2 pathway by coffee extracts - PubMed (original) (raw)

Cell‑specific and roasting‑dependent regulation of the Keap1/Nrf2 pathway by coffee extracts

Alexandros Priftis et al. Mol Med Rep. 2018 Jun.

Abstract

Coffee is a popular beverage that contains various bioactive compounds. However, its molecular mechanism of action is not fully elucidated. In this context, two previously characterized coffee extracts, a lightly roasted and the corresponding green one, were investigated for their effect on nuclear factor erythroid 2‑related factor 2 (Nrf2) target gene expression in myoblasts and endothelial cells using quantitative PCR. The tested concentrations were non‑cytotoxic and led to improved redox cell status, as was evident by increased reduced glutathione (GSH) levels. In both cell lines, the roasted extract upregulated gene expression more readily than its green counterpart leading to increased NAD(P)H quinone dehydrogenase 1 and γ‑glutamyl cysteine ligase catalytic subunit, among others. The green extract had a mixed effect on the endothelial cells, while, as regards the myoblasts it caused the downregulation of some Nrf‑target genes. Therefore, a potential dose‑ and roasting‑dependent mechanism is proposed in the current study, accounting for coffee's antioxidant activity.

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Figures

Figure 1.

Figure 1.

Effect of the tested coffee extracts on Nrf2 target-gene expression in C2C12 cells. qPCR results are depicted, following administration of coffee extracts on myoblasts for 3, 12 or 24 h. Gene expression has been normalised using gapdh expression and the fold-change in gene expression in comparison to the control cells (black bars) is displayed. The results are expressed as mean ± SD and the asterisk (*) symbolises statistical significance at the P<0.05 level. Nrf2, nuclear factor erythroid 2-related factor 2.

Figure 2.

Figure 2.

Effect of the tested coffee extracts on Nrf2 target-gene expression in EA.hy926 cells. qPCR results are depicted, following administration of coffee extracts on endothelial cells for 3, 12 or 24 h. Gene expression has been normalised using gapdh expression and the fold-change in gene expression in comparison to the control cells (black bars) is displayed. The results are expressed as mean ± SD and the asterisk (*) symbolises statistical significance at the P<0.05 level. Nrf2, nuclear factor erythroid 2-related factor 2.

Figure 3.

Figure 3.

Suggested dose-dependent mechanism of action for the CGAs present in coffee. The potential mechanism of action of the tested coffee extracts is displayed. Their effect on the myoblasts and endothelial cells is dependent on CGA concentration. Low doses (as is the case for the green extract) exert a direct free radical scavenging activity sparing endogenous GSH levels, while at higher doses (as is the case for the roasted extract) Nrf2 derepression occurs, leading to the expression of its target genes. At higher doses, toxicity ensues, possibly due to the pro-oxidant effect of polyphenols. CGA, chlorogenic acids; GSH, glutathione; Nrf2, nuclear factor erythroid 2-related factor 2.

References

    1. Ray PD, Huang BW, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal. 2012;24:981–990. doi: 10.1016/j.cellsig.2012.01.008. - DOI - PMC - PubMed
    1. Halliwell B. eLS. John Wiley & Sons, Ltd.; Hoboken, NJ: 2001. Free radicals and other reactive species in disease.
    1. Sosa V, Moliné T, Somoza R, Paciucci R, Kondoh H, LLeonart ME. Oxidative stress and cancer: An overview. Ageing Res Rev. 2013;12:376–390. doi: 10.1016/j.arr.2012.10.004. - DOI - PubMed
    1. Rochette L, Zeller M, Cottin Y, Vergely C. Diabetes, oxidative stress and therapeutic strategies. Biochim Biophys Acta. 2014;1840:2709–2729. doi: 10.1016/j.bbagen.2014.05.017. - DOI - PubMed
    1. Veskoukis AS, Goutianos G, Paschalis V, Margaritelis NV, Tzioura A, Dipla K, Zafeiridis A, Vrabas IS, Kyparos A, Nikolaidis MG. The rat closely mimics oxidative stress and inflammation in humans after exercise but not after exercise combined with vitamin C administration. Eur J Appl Physiol. 2016;116:791–804. doi: 10.1007/s00421-016-3336-8. - DOI - PubMed

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