Sumio Hirata

Publications (2)1.66 Total impact

• Article: Phosphoenolpyruvate, a glycolytic intermediate, as a cytoprotectant and antioxidant in ex-vivo cold-preserved mouse liver: a potential application for organ preservation.

  Yuki Kondo, Yoichi Ishitsuka, Daisuke Kadowaki, Yusuke Fukumoto, Yohei Miyamoto, Mitsuru Irikura, Sumio Hirata, Keizo Sato, Toru Maruyama, Naotaka Hamasaki, Tetsumi Irie
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  ABSTRACT: The aim of this study was to examine the effect of phosphoenolpyruvate (PEP), a glycolytic intermediate, on organ damage during cold preservation of liver. An ex-vivo mouse liver cold-preservation model and an in-vitro liver injury model induced by hydrogen peroxide in HepG2 cells were leveraged. PEP attenuated the elevation of aminotransferases and lactate dehydrogenase leakage during organ preservation, histological changes and changes in oxidative stress parameters (measured as thiobarbituric acid reactive substance and glutathione content) induced by 72 h of cold preservation of the liver. The effects were comparable with the University of Wisconsin solution, a gold standard organ preservation agent. The decrease in ATP content in liver during the cold preservation was attenuated by PEP treatment. PEP prevented the cellular injury and increases in intracellular reactive oxygen species in HepG2 cells. In addition, PEP scavenged hydroxyl radicals, but had no effect on superoxide anion as evaluated by an electron paramagnetic resonance spin-trapping technique. PEP significantly attenuated the injury, oxidative stress and ATP depletion in liver during cold preservation. The antioxidative potential of PEP was confirmed by in-vitro examination. We suggest that PEP acts as a glycolytic intermediate and antioxidant, and is particularly useful as an organ preservation agent in clinical transplantation.
  The Journal of pharmacy and pharmacology. 03/2013; 65(3):390-401.
• Article: Phosphoenolpyruvic acid, an intermediary metabolite of glycolysis, as a potential cytoprotectant and anti-oxidant in HeLa cells.

  Yuki Kondo, Yoichi Ishitsuka, Daisuke Kadowaki, Masataka Kuroda, Yuta Tanaka, Minako Nagatome, Mitsuru Irikura, Sumio Hirata, Keizo Sato, Toru Maruyama, Naotaka Hamasaki, Tetsumi Irie
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  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.
  Biological & Pharmaceutical Bulletin 01/2012; 35(4):606-11. · 1.66 Impact Factor