Inhibition of hexokinase leads to neuroprotection against excitotoxicity in organotypic hippocampal slice culture

Authors

  • Kyung Hee Lee,

    1. Department of Dental Hygiene, Division of Health Science, Dongseo University, Busan, Korea
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  • Ji Ho Park,

    1. Department of Neuroscience, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Korea
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  • Ran Won,

    1. Department of Dental Hygiene, Division of Health Science, Dongseo University, Busan, Korea
    2. Department of Biomedical Laboratory Science, Division of Health Science, Dongseo University, Busan, Korea
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  • Hyejung Lee,

    1. Acupuncture and Meridian Science Research Center, Kyung Hee University, Seoul, Korea
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  • Taick Sang Nam,

    1. Department of Physiology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
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  • Bae Hwan Lee

    Corresponding author
    1. Department of Physiology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
    • Bae Hwan Lee, PhD, Department of Physiology, Yonsei University College of Medicine, C.P.O. Box 8044, Seoul 120-752, Republic of Korea
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Abstract

During seizures, glucose concentrations are high in the hippocampus. Mitochondrial hexokinase (HK) catalyzes the first essential step of glucose metabolism and directly couples extramitochondrial glycolysis to intramitochondrial oxidative phosphorylation. The neuroprotective effects of an HK inhibitor, 3-bromopyruvate (3-BrPA), on kainic acid (KA)-induced excitotoxic injury were investigated. Hippocampal slices were prepared from hippocampi of 6–8-day-old rats using a tissue chopper and placed on a membrane insert. After a treatment with KA (5 μM) for 15 hr, neuronal death was quantified by propidium iodide (PI), cresol violet, and TUNEL staining. KA-induced cell death was significantly prevented by 30 μM 3-BrPA treatment. According to Western blots, the expression level of phospho-Akt increased after 3-BrPA treatment. The induction of long-term potentiation (LTP) at 48 hr after 3-BrPA treatment tended to increase in the CA1 area compared with the KA-only group, but the difference was not significant. Blocking the PI3 kinase/Akt pathway using LY294002 reversed the neuroprotective effect of 3-BrPA. These results suggest that inhibition of HK may play a protective role against neuronal death in KA-induced excitotoxic injury. © 2010 Wiley-Liss, Inc.

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