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Activation of the pentose phosphate pathway by microcurrent stimulation mediates antioxidant effects in
Mikiko Uemura1,2, Noriaki Maeshige1, Atomu Yamaguchi1,3
1Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences, Kobe, Japan.
Introduction:
Excessive inflammatory responses in macrophages lead to increased oxidative stress, and the excessive production of reactive oxygen species (ROS) causes tissue damage, contributing to the development of chronic diseases and tissue deterioration. Therefore, controlling the inflammatory response and ROS production is crucial for human health. Electrical stimulation (ES) has been shown to have antioxidant and anti-inflammatory effects on macrophages. However, the key pathway underlying these effects remains unclear.
Methods:
In this study, ES was applied to Lipopolysaccharide (LPS)-stimulated macrophages, and the production of ROS and 8-hydroxy-2'-deoxyguanosine (8-OHdG), inflammatory cytokine expression, and intracellular metabolites were analyzed in a glucose-6-phosphate dehydrogenase (G6PD) knockdown experiment, the rate-limiting enzyme of the Pentose Phosphate Pathway(PPP).
Results:
ES significantly increased sedoheptulose 7-phosphate (S7P), an intermediate metabolite in PPP, and reduced ROS and 8-OHdG production and the expression of inflammatory cytokines in LPS-stimulated macrophages. Meanwhile, ES did not exert antioxidant effects in G6PD-knockdown macrophages.
Discussion:
These findings indicate that the antioxidant effects of ES are mediated by PPP in LPS-stimulated macrophages.
Insights
Electrical stimulation (ES) reduces oxidative stress and inflammation in macrophages by activating the Pentose Phosphate Pathway (PPP). This pathway is key to ES
Area of Science:
- Cell Biology
- Biochemistry
- Immunology
Background:
- Macrophage inflammatory responses drive oxidative stress and tissue damage, contributing to chronic diseases.
- Controlling reactive oxygen species (ROS) and inflammation is vital for health.
- Electrical stimulation (ES) shows promise for antioxidant and anti-inflammatory effects, but the underlying mechanisms are unclear.
Purpose of the Study:
- To investigate the key pathway mediating the antioxidant and anti-inflammatory effects of ES on macrophages.
- To elucidate the role of the Pentose Phosphate Pathway (PPP) in ES-induced cellular protection.
Main Methods:
- Lipopolysaccharide (LPS)-stimulated macrophages were treated with ES.
- ROS and 8-hydroxy-2'-deoxyguanosine (8-OHdG) production, inflammatory cytokine expression, and intracellular metabolites were analyzed.
- Experiments included glucose-6-phosphate dehydrogenase (G6PD) knockdown to assess the Pentose Phosphate Pathway (PPP) involvement.
Main Results:
- ES significantly increased sedoheptulose 7-phosphate (S7P), a PPP intermediate metabolite.
- ES reduced ROS and 8-OHdG production and inflammatory cytokine expression in LPS-stimulated macrophages.
- ES's antioxidant effects were abolished in G6PD-knockdown macrophages, indicating PPP dependence.
Conclusions:
- The antioxidant effects of electrical stimulation (ES) on macrophages are mediated by the Pentose Phosphate Pathway (PPP).
- Targeting the PPP could be a therapeutic strategy for conditions involving oxidative stress and inflammation.
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