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. 2024 Jun 20;16(12):1966.
doi: 10.3390/nu16121966.

Selenomethionine Inhibited HADV-Induced Apoptosis Mediated by ROS through the JAK-STAT3 Signaling Pathway

Chuqing Li  1 , Xia Liu  1 , Jiali Li  1 , Jia Lai  1 , Jingyao Su  1 , Bing Zhu  1 , Buyun Gao  2 , Yinghua Li  1 , Mingqi Zhao  1
Affiliations

Selenomethionine Inhibited HADV-Induced Apoptosis Mediated by ROS through the JAK-STAT3 Signaling Pathway

Chuqing Li et al. Nutrients. .

Erratum in

Abstract

Adenovirus (HAdV) can cause severe respiratory infections in children and immunocompromised patients. There is a lack of specific therapeutic drugs for HAdV infection, and the study of anti-adenoviral drugs has far-reaching clinical implications. Elemental selenium can play a specific role as an antioxidant in the human immune cycle by non-specifically binding to the amino acid methionine in body proteins. Methods: The antiviral mechanism of selenomethionine was explored by measuring cell membrane status, intracellular DNA status, cytokine secretion, mitochondrial membrane potential, and ROS production. Conclusions: Selenomethionine improved the regulation of ROS-mediated apoptosis by modulating the expression of Jak1/2, STAT3, and BCL-XL, which led to the inhibition of apoptosis. It is anticipated that selenomethionine will offer a new anti-adenoviral therapeutic alternative.

Keywords: ROS; adenovirus; apoptosis; selenomethionine.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1
Selenomethionine’s optimal low-toxicity antiviral concentration in A549 cells. (A) Changes in the status of HAdV-7-infected A549 cells show the antiviral capacity of selenomethionine in the concentration range of 8–32 μM. (B) Fluorescence changes in rAD7EGFP-infected A549 cells showing the antiviral ability of selenomethionine in the concentration range of 8–32 μM. (C) The CCK-8 assay detects the viability of selenomethionine in the concentration range of 2–32 μM on A549 cells. (D) The viability of HAdV-7-infected A549 cells as detected by the CCK-8 assay increased with increasing concentrations of selenomethionine in the 8–32 μM concentration range. Error lines indicate the mean ± standard deviation (n = 3), and confidence intervals are at a 95% level. Differences between data were statistically significant when p < 0.05 (*), p < 0.01 (**), p < 0.001 (***), or p < 0.0001 (****).
Figure 2
Figure 2
Selenomethionine’s inhibitory action on DNA damage and apoptosis brought on by HAdV-7 infection. (A) Results of cells stained with Annexin V-FITC and PI from several experimental groups. Phosphatidylserine translocation and A549 cell membrane’s permeability were found using fluorescence microscopy. (B) Results of cells in different experimental groups stained with TUNEL-DAPI double staining. DNA damage and nucleus deformation in A549 cells were detected by fluorescence microscopy. Concentrations of SeC were 8 μM, 16 μM, and 32 μM, respectively.
Figure 3
Figure 3
Selenomethionine repairs mitochondrial dysfunction induced by HAdV-7 infection. (A) The JC-1 Mitochondrial Membrane Potential Assay Kit was utilized to identify alterations in mitochondrial membrane potential, while a fluorescence microscope was employed to observe changes in fluorescence. (B) The quantification of cells with different fluorescence intensities by flow cytometry. The concentration of selenomethionine were 8 μM, 16 μM, and 32 μM, in that order.
Figure 4
Figure 4
Selenomethionine reduces HAdV-7 infection-induced ROS overproduction. (A) An optical microscope was used to observe the cell morphology of different experimental groups and fluorescence microscope to detect the production of ROS. (B) Using a fully automated enzyme labeler, the absorbance was determined at a 488 nm excitation wavelength and 525 nm emission wavelength. The level of ROS was shown by the fluorescence intensity. The concentration of selenomethionine were 8 μM, 16 μM, and 32 μM, in that order. p < 0.0001 (****) indicates that the difference is statistically significant.
Figure 5
Figure 5
The level of cytokines released by A549 cells infected with HAdV-7 is regulated by selenomethionine. The levels of IL-8, IL-10, IL-6, TNF-α, and IFN-γ that cells in various experimental groups secreted. The concentrations of selenomethionine were 8 μM, 16 μM, and 32 μM, respectively. p < 0.05 (*), p < 0.01 (**), p < 0.001 (***), and p < 0.0001 (****) indicated that the differences were statistically significant.
Figure 6
Figure 6
The inhibition of apoptosis signaling pathways by selenomethionine. (A) Selenomethionine inhibits HAdV-7-induced apoptosis through the JAK-STAT3 signaling pathway mediated by ROS. The concentrations of selenomethionine were 32 μM. (B) A diagram of the mechanism by which selenomethionine exhibits anti-HAdV-7 activity by modulating apoptotic signaling pathways.
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