Document Detail

Protective effect of nicotinamide on neuronal cells under oxygen and glucose deprivation and hypoxia/reoxygenation.
MedLine Citation:
PMID:  15153782     Owner:  NLM     Status:  MEDLINE    
Nicotinamide (vitamin B(3)) reduces the infarct volume following focal cerebral ischemia in rats; however, its mechanism of action has not been reported. After cerebral ischemia and/or reperfusion, reactive oxygen species (ROS) and reactive nitrogen species may be generated by inflammatory cells through several cellular pathways, which can lead to intracellular calcium influx and cell damage. Therefore, we investigated the mechanisms of action of nicotinamide in neuroprotection under conditions of hypoxia/reoxygenation. Results showed that nicotinamide significantly protected rat primary cortical cells from hypoxia by reducing lactate dehydrogenase release with 1 h of oxygen-glucose deprivation (OGD) stress. ROS production and calcium influx in neuronal cells during OGD were dose-dependently diminished by up to 10 mM nicotinamide (p < 0.01). This effect was further examined with OGD/reoxygenation (H/R). Cells were stained with the fluorescent dye 4,6-diamidino-2-phenylindole (DAPI) or antibodies against anti-microtubule-associated protein-2 and cleaved caspase-3. Apoptotic cells were studied using Western blotting of cytochrome c and cleaved caspase-3. Results showed that vitamin B(3) reduced cell injury, caspase-3 cleavage and nuclear condensation (DAPI staining) in neuronal cells under H/R. In addition, nicotinamide diminished c-fos and zif268 immediate-early gene expressions following OGD. Taken together, these results indicate that the neuroprotective effect of nicotinamide might occur through these mechanisms in this in vitro ischemia/reperfusion model.
Chiung-Chyi Shen; Hsueh-Meei Huang; Hsiu-Chung Ou; Huan-Lian Chen; Wen-Chi Chen; Kee-Ching Jeng
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of biomedical science     Volume:  11     ISSN:  1021-7770     ISO Abbreviation:  J. Biomed. Sci.     Publication Date:    2004 Jul-Aug
Date Detail:
Created Date:  2004-05-21     Completed Date:  2005-03-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421567     Medline TA:  J Biomed Sci     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  472-81     Citation Subset:  IM    
Copyright Information:
Copyright 2004 National Science Council, ROC and S. Karger AG, Basel
Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
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MeSH Terms
Brain Ischemia / prevention & control*
Calcium / metabolism
Caspase 3
Caspases / metabolism
Cells, Cultured
Cerebral Cortex / cytology
Glucose / metabolism
L-Lactate Dehydrogenase / metabolism
Models, Biological
Neurons / drug effects*,  metabolism*,  pathology
Niacinamide / pharmacology*
Oxygen / metabolism
Protective Agents / pharmacology
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism
Reg. No./Substance:
0/Protective Agents; 0/Reactive Oxygen Species; 50-99-7/Glucose; 7440-70-2/Calcium; 7782-44-7/Oxygen; 98-92-0/Niacinamide; EC Dehydrogenase; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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