Molecular insight into the docking of lysophosphatidylethanolamine (lysoPE)-22:6 interaction with GPR119: Acute exposure to an electric field induces changes in human plasma lysoPE-22:6 and lysoPE-20:4 levels

Abstract

Medical treatment using high-voltage electric potential (HELP) devices to generate an electric field (EF) is an alternative therapy commonly used in Japan. However, the underlying mechanisms of the potential health benefits of this therapy are not fully understood. Therefore, we investigated the lysophosphatidylethanolamine (lysoPE) and lysophosphatidylinositol (lysoPI) levels using selected reaction monitoring (SRM) analysis in plasma samples obtained from healthy human subjects before and after exposure to a single HELP exposure (9 kV/electrode + 9 kV/electrode, 30 min). LysoPE-22:6 and lysoPE-20:4 were significantly upregulated after HELP exposure. However, there were no effects on the levels of phosphatidylethanolamine (PE) and phosphatidylinositol (PI), lysoPI, or other lysoPE species. LysoPE is known to activate G protein-coupled receptor 119 (GPR119). No X-ray crystal structure has been reported for GPR119; thus we examined the in silico docking simulation of lysoPE-22:6 with GPR119 using a homology model. LysoPE-22:6 showed strong interaction energy of -10.603 kcal/mol. Our findings provide new insight into the molecular mechanisms of the health benefits of EF therapy.

Acute electric field downregulates human plasma immunoreactive interleukin-6 and -1β levels: Molecular mechanisms underlying inflammation alleviation through electric field therapy

“…Thus, at present, it is not possible to investigate the effect of lysoPC-22:4 on the intracellular levels of calcium in CHO-K1 or HEK293T cells stably expressing hTRPM8. An increasing number of reports on virtual simulation are available in the literature [25,28,34]. Studies involving in silico molecular docking have been conducted to support the pharmacological results.…”

“…Once the crystal structure of TRPM8 is determined, it may be interesting to identify the binding pocket of lysoPC-22:4, lysoPE-20:4, and lysoPE-22:6 in hTRPM8. However, lysoPC-22:4, lysoPE-20:4, and lysoPE-22:6 also activate the G protein-coupled receptor 119, raising the possibility that these receptors may serve as targets for lysoPC-22:4, lysoPE-20:4, and lysoPE-22:6 during EF exposure [25].…”

“…Our previous attempts to identify biomarker induced by HELP exposure using plasma metabolomics and lipidomics have led to the detection of lipid-derived signaling molecules such as 3-hydroxybutyrate (3-HBA), cis-8,11,14-eicosatrienoic acid, 9-hydroxyoctadecadienoic acid (9-HODE), 13-hydroxyoctadecadienoic acid (13-HODE), oleoylethanolamide (OEA), lysophosphatidylethanolamine (lysoPE)-20:4, and lysoPE-22:6 [21][22][23][24][25]. Endogenous lipid-derived signaling molecules have been suggested as candidate molecules, representing the interface between symptoms and electroceutical target proteins [21][22][23][24][25][26]. A recent study conducted by Smani et al reported that pretreatment with lysophosphatidylcholine (lysoPC) induced decreases in the levels of pro-inflammatory cytokines in the murine model of peritoneal sepsis caused by Acinetobacter baumannii [27].…”

Targeted lipidomics reveals changes in N-acyl serines by acute exposure to an electric field: Molecular insights into the docking of N-18:1 serine interaction with TRPV1 or PPAR-α

“…High-voltage electric field (EF) therapy may be an effective treatment for shoulder stiffness, headache, insomnia, and chronic constipation [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Although EF therapy was discovered about 90 years ago, the molecular mechanisms associated with its health benefits remain elusive.…”

“…Although EF therapy was discovered about 90 years ago, the molecular mechanisms associated with its health benefits remain elusive. A therapeutic device that exposes the human body to high-voltage electric potential (HELP) was approved by the Ministry of Health, Labour and Welfare in Japan [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. A review of the literature suggests that HELP exposure may be an alternative therapy for several conditions.…”