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Effects of sodium metabisulfite on pyroptosis, mitophagy and degranulation in mast cells
Meitong Liu1, Jing Lu2, Qingbin Liu3
1College of Food Science and Engineering, Jilin University, Changchun, Jilin, 130062, China.
Abstract:
Sodium metabisulphite (SMB) is the most used foods and drugs antioxidant among sulfites. So far, there were few studies about its harm, especially in mast cells. Our study was to investigate the effects of SMB on mitophagy and pyroptosis in mast cells. The results revealed that SMB dose-dependently promoted the expressions of NLRP3, GSDMD-N and other marker proteins of pyroptosis. Knockdown of GSDMD, NLRP3 inhibitor, mitophagy activator and mtROS inhibitor all reversed the changes in pyroptosis indicators caused by SMB. Considering the degranulation characteristics of mast cells and the sensitization of sulfite, we examined the effects of the above inhibitors on the degranulation of mast cells caused by SMB. The results showed that SMB-mediated mast cell degranulation was significantly inhibited by the above inhibitors. Meanwhile, we used immunofluorescence co-localization experiments and found that GSDMD pore-forming protein and histamine co-localized near the cell membrane. Overall, evidence suggested that SMB caused pyroptosis by inhibiting mitophagy, leading to mast cell degranulation. These findings are of great significance to the sensitization mechanism of SMB and provide a new insight into SMB toxicology and mast cell degranulation.
Insights
Sodium metabisulphite (SMB) triggers pyroptosis and mast cell degranulation by inhibiting mitophagy. Interventions targeting pyroptosis and mitophagy pathways can mitigate SMB-induced mast cell responses.
Area of Science:
- Food toxicology
- Immunology
- Cellular biology
Background:
- Sodium metabisulphite (SMB) is a widely used antioxidant in food and drugs.
- Limited research exists on SMB's adverse effects, particularly on mast cells.
- Mast cells play crucial roles in allergic reactions and immune responses.
Purpose of the Study:
- To investigate the impact of SMB on mitophagy and pyroptosis in mast cells.
- To elucidate the mechanisms underlying SMB-induced mast cell degranulation.
- To explore potential therapeutic targets for SMB sensitization.
Main Methods:
- Dose-dependent analysis of SMB effects on mast cell pyroptosis markers (NLRP3, GSDMD-N).
- Genetic and pharmacological interventions: GSDMD knockdown, NLRP3 inhibition, mitophagy activation, mtROS inhibition.
- Assessment of mast cell degranulation and co-localization of GSDMD with histamine via immunofluorescence.
Main Results:
- SMB promoted pyroptosis markers in a dose-dependent manner.
- Inhibitors of pyroptosis, mitophagy, and mtROS reversed SMB-induced pyroptosis.
- SMB-induced mast cell degranulation was significantly reduced by these inhibitors.
- GSDMD and histamine were found co-localized near the cell membrane.
Conclusions:
- SMB induces mast cell pyroptosis by inhibiting mitophagy, leading to degranulation.
- These findings offer insights into SMB sensitization mechanisms and toxicology.
- Targeting pyroptosis and mitophagy pathways may mitigate SMB-induced mast cell degranulation.
