Proteomic identification of proteins differentially expressed by nicotinamide in focal cerebral ischemic injury.
Nicotinamide exerts a potent neuroprotective effect against ischemia-induced brain injury. We identified proteins that were differentially expressed by nicotinamide treatment in ischemic brain injury. Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO). Adult male Sprague-Dawley rats were treated with vehicle or nicotinamide (500 mg/kg) 2 h after the onset of MCAO. Brains were collected 24 h after MCAO and cerebral cortex regions were isolated. Protein spots with different intensities between vehicle- and nicotinamide-treated groups were detected using two-dimensional gel electrophoresis and identified by mass spectrometry. Among these proteins, γ-enolase, protein phosphatase 2A (PP2A) subunit B, and peroxiredoxin-2 (Prx-2) were significantly decreased in the vehicle-treated group compared to the nicotinamide-treated group. These identified proteins mediate cell differentiation and stabilization, and play a role as antioxidant enzymes. In contrast, 60 kDa heat shock protein (Hsp 60) was significantly increased in vehicle-treated animals, while nicotinamide prevented the injury-induced increase of this protein. These results suggest that nicotinamide mediates neuroprotective effects by up- and down-regulation of various specific proteins.
Department of Anatomy, College of Veterinary Medicine and Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, South Korea.
J-H
JH
Sung
M-O
MO
Kim
P-O
PO
Koh
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D018834:Chaperonin 60 / Q000096:biosynthesis; D015180:Electrophoresis, Gel, Two-Dimensional; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009536:Niacinamide / Q000494:pharmacology*; D054464:Peroxiredoxins / Q000096:biosynthesis; D010751:Phosphopyruvate Hydratase / Q000096:biosynthesis; D054648:Protein Phosphatase 2 / Q000096:biosynthesis; D020543:Proteome / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018834:Chaperonin 60; D018696:Neuroprotective Agents; D020543:Proteome; D009536:Niacinamide; D054464:Peroxiredoxins; D054648:Protein Phosphatase 2; D010751:Phosphopyruvate Hydratase