Electrical stimulation facilitates NADPH production in pentose phosphate pathway and exerts an anti-inflammatory effect in macrophages

• Published in: Scientific reports 2023-10, Vol.13 (1), p.17819-17819, Article 17819
• Main Authors: Uemura, Mikiko, Maeshige, Noriaki, Yamaguchi, Atomu, Ma, Xiaoqi, Matsuda, Mami, Nishimura, Yuya, Hasunuma, Tomohisa, Inoue, Taketo, Yan, Jiawei, Wang, Ji, Kondo, Hiroyo, Fujino, Hidemi
• Format: Article
• Language: English
• Subjects: 631/250; 692/700; Bone marrow; Capillary electrophoresis; Cytokines; Effector cells; Electrical stimuli; Glucose-1-phosphate; Glycogen; Glycolysis; Humanities and Social Sciences; Immune system; Inflammation; Innate immunity; Ketoglutaric acid; Lipopolysaccharides; Macrophages; Mass spectrometry; Mass spectroscopy; Metabolism; Metabolites; multidisciplinary; NADPH-diaphorase; Oxidative stress; Pentose phosphate pathway; Phosphates; Reactive oxygen species; Science; Science (multidisciplinary); Tricarboxylic acid cycle
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-44886-x

Macrophages play an important role as effector cells in innate immune system. Meanwhile, macrophages activated in a pro-inflammatory direction alter intracellular metabolism and damage intact tissues by increasing reactive oxygen species (ROS). Electrical stimulation (ES), a predominant physical agent to control metabolism in cells and tissues, has been reported to exert anti-inflammatory effect on immune cells. However, the mechanism underlying the anti-inflammatory effects by ES is unknown. This study aimed to investigate the effect of ES on metabolism in glycolytic-tricarboxylic acid cycle (TCA) cycle and inflammatory responses in macrophages. ES was performed on bone marrow-derived macrophages and followed by a stimulation with LPS. The inflammatory cytokine expression levels were analyzed by real-time polymerase chain reaction and ELISA. ROS production was analyzed by CellRox Green Reagent and metabolites by capillary electrophoresis-mass spectrometry. As a result, ES significantly reduced proinflammatory cytokine expression levels and ROS generation compared to the LPS group and increased glucose-1-phosphate, a metabolite of glycogen. ES also increased intermediate metabolites of the pentose phosphate pathway (PPP); ribulose-5-phosphate, rebose-5 phosphate, and nicotinamide adenine dinucleotide phosphate, a key factor of cellular antioxidation systems, as well as α-Ketoglutarate, an anti-oxidative metabolite in the TCA cycle. Our findings imply that ES enhanced NADPH production with enhancement of PPP, and also decreased oxidative stress and inflammatory responses in macrophages.