title: Phosphoenolpyruvic acid, an intermediary metabolite of glycolysis, as a potential cytoprotectant and anti-oxidant in HeLa cells.
abstract: This study examined the cytoprotective and anti-oxidative properties of phosphoenolpyruvic acid (PEP), a glycolysis metabolite with a high-energy phosphate group. PEP (0.1-10 mM) significantly attenuated the decrease in cell viability induced by hydrogen peroxide (H(2)O(2)) in HeLa cells in a dose-dependent manner. PEP also inhibited the decrease in calcein-acetomethoxy-stained cells and the increase in propidium iodide-stained cells that were induced by H(2)O(2). The H(2)O(2)-stimulated increase in intracellular reactive oxygen species was significantly reduced by PEP. PEP also demonstrated scavenging potential against hydroxyl radicals, as assessed by the electron paramagnetic resonance method. In addition, PEP demonstrated scavenging potential against the 1,1-diphenyl-2-picrylhydrazyl radical, a representative artificial radical, although the potential is very weak. PEP (10 mM) slightly inhibited the decrease in cellular ATP content induced by H(2)O(2), but did not show any effects at low doses (0.1, 1 mM). PEP (0.1-10 mM) also attenuated the cell injury but not the decrease in intracellular ATP content, induced by 2-deoxy-D-glucose, a glycolysis inhibitor. These results indicate that PEP exerts cytoprotective effects and has anti-oxidative potential, although the precise cytoprotective mechanisms are not fully elucidated. We suggest that PEP is a functional carbohydrate metabolite with cytoprotective and anti-oxidative activity, and is potentially useful as a therapeutic agent against diseases that involve the oxidative stress.
authors.affiliation: Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kondo
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ishitsuka
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kadowaki
authors.forename: Masataka
authors.initials: M
authors.lastname: Kuroda
authors.forename: Yuta
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Minako
authors.initials: M
authors.lastname: Nagatome
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Irikura
authors.forename: Sumio
authors.initials: S
authors.lastname: Hirata
authors.forename: Keizo
authors.initials: K
authors.lastname: Sato
authors.forename: Toru
authors.initials: T
authors.lastname: Maruyama
authors.forename: Naotaka
authors.initials: N
authors.lastname: Hamasaki
authors.forename: Tetsumi
authors.initials: T
authors.lastname: Irie
mesh_terms: D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D003847:Deoxyglucose / Q000494:pharmacology; D006019:Glycolysis; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D010728:Phosphoenolpyruvate / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D016877:Oxidants; C055833:phosphoenolthiopyruvate; D010728:Phosphoenolpyruvate; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D006861:Hydrogen Peroxide