Identification of proteins differentially expressed by melatonin treatment in cerebral ischemic injury--a proteomics approach.
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, gamma-enolase, stathmin, thioredoxin, peroxiredoxin-6, hippocalcin, protein phosphatase 2A, adenosylhomocysteinase, ubiquitin carboxy-terminal hydrolase L1, and NAD-specific isocitrate dehydrogenase subunit alpha 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.
Sung
Jin-Hee
JH
Department of Anatomy, College of Veterinary Medicine and Research Institute of Life Science, Gyeongsang National University, Jinju, South Korea.
Cho
Eun-Hae
EH
Kim
Myeong-Ok
MO
Koh
Phil-Ok
PO
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D003627:Data Interpretation, Statistical; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation / Q000187:drug effects*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000494:pharmacology* / Q000627:therapeutic use; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D040901:Proteomics; D051381:Rats
D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; C095114:collapsin response mediator protein-2; D008550:Melatonin