title: Nicotinamide prevents the down-regulation of MEK/ERK/p90RSK signaling cascade in brain ischemic injury.
abstract: Nicotinamide attenuates neuronal cell death related to focal cerebral ischemic injury. This study investigated whether nicotinamide exerts a neuroprotective effect through the activation of Raf- mitogen-activated protein kinase kinase (MEK)-ERK and its downstream targets, including p90 ribosomal S6 kinase (p90RSK) and Bad. Adult male Sprague-Dawley rats were treated with nicotinamide (500 mg/kg) or vehicle 2 hr after the onset of middle cerebral artery occlusion (MCAO). Brains were collected 24 hr after MCAO. In the present study, nicotinamide significantly reduces the volume of infarct regions and decreases the number of positive cells by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining in the cerebral cortex. Nicotinamide prevents injury-induced decrease in Raf-1, MEK1/2, and ERK1/2 phosphorylation. As part of the downstream cascade, nicotinamide inhibits the injury-induced decrease in p90RSK and Bad phosphorylation. Moreover, nicotinamide prevents the injury-induced increase in cleaved caspase-3 levels. These findings suggest that nicotinamide protects neuronal cells against cerebral ischemic injury and that MEK-ERK-p90RSK cascade activation by nicotinamide contributes to these neuroprotective effects.
authors: Department of Anatomy, College of Veterinary Medicine and Research Institute of Life Science, Gyeongsang National University, Jinju, South Korea.
authors: Jin-Hee
authors: JH
authors: Sung
authors: Myeong-Ok
authors: MO
authors: Kim
authors: Phil-Ok
authors: PO
authors: Koh
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000201:enzymology / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy*; D002544:Cerebral Infarction / Q000517:prevention & control; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009536:Niacinamide / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism*; D014803:Vitamin B Complex / Q000627:therapeutic use*
chemical_list: D014803:Vitamin B Complex; D009536:Niacinamide; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases