Identification of proteins differentially expressed by melatonin treatment in cerebral ischemic injury – a proteomics approach

Authors

  • Jin-Hee Sung,

    1. Department of Anatomy, College of Veterinary Medicine and Research Instituite of Life Science
    2. Division of Life Science and Applied Life Science (Brain Korea 21), Gyeongsang National University, Jinju, South Korea
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    • *

      Both these authors contributed equally to this study.

  • Eun-Hae Cho,

    1. Department of Anatomy, College of Veterinary Medicine and Research Instituite of Life Science
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    • *

      Both these authors contributed equally to this study.

  • Myeong-Ok Kim,

    1. Division of Life Science and Applied Life Science (Brain Korea 21), Gyeongsang National University, Jinju, South Korea
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  • Phil-Ok Koh

    1. Department of Anatomy, College of Veterinary Medicine and Research Instituite of Life Science
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Address reprint requests to Phil-Ok Koh, PhD, DVM, Department of Anatomy, College of Veterinary Medicine, Gyeongsang National University, 900 Gajwa-dong, Jinju 660-701, South Korea.
E-mail: pokoh@gsnu.ac.kr

Abstract

Abstract:  We previously reported that melatonin protects neuronal cells against ischemic brain damage. In this study, we identified proteins that were differentially expressed by melatonin treatment during ischemic brain injury. Rats were subjected to cerebral ischemia by middle cerebral artery occlusion (MCAO). Adult male rats were treated with melatonin (5 mg/kg) or vehicle prior to MCAO and brains were collected at 24 hr after MCAO. Proteins derived from the cerebral cortex were analyzed using two-dimensional gel electrophoresis. Protein spots with a greater than 2.5-fold change in intensity were identified by mass spectrometry. Among these proteins, γ-enolase, stathmin, thioredoxin, peroxiredoxin-6, hippocalcin, protein phosphatase 2A, adenosylhomocysteinase, ubiquitin carboxy-terminal hydrolase L1, and NAD-specific isocitrate dehydrogenase subunit α were significantly decreased in the vehicle-treated group in comparison to the melatonin-treated group. The identified proteins consist of cell differentiation and stabilization proteins, as well as an antioxidant enzyme. In contrast, dehydroprimidinase-related protein 2 (DRP-2), a target of protein oxidation in neurodegeneration, was significantly increased in vehicle-treated animals, while melatonin prevented the injury-induced increase of DRP-2. Thus, the results of this study suggest that melatonin prevents cell death resulting from ischemic brain injury and that its neuroprotective effects are mediated by both the up- and down-regulation of various proteins.

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