title: Nicotinamide: A Nutritional Supplement that Provides Protection Against Neuronal and Vascular Injury.
abstract: In addition to functioning as an essential nutrient for cellular growth and maintenance, nicotinamide also may be an attractive therapeutic agent with efficacy demonstrated against free radical ischemic programmed cell death (PCD). Yet, the cellular mechanisms that mediate cellular PCD, as well as protection by nicotinamide, are considered to require further definition. In primary rat hippocampal neurons and rat cerebrovascular endothelial cells (ECs), cellular injury was determined through trypan blue dye exclusion, externalization of membrane phosphatidylserine (PS) residues, and activation of the mitogen-activated protein kinase p38 through Western blot analysis. Nicotinamide was without cellular toxicity at concentrations lower than 50 mM in both neuronal and EC populations. Exposure to either anoxia or the nitric oxide (NO) donors sodium nitroprusside and NOC-9 significantly decreased neuronal and EC survival from approximately 85% to 38% and increased membrane PS exposure from approximately 10% to 80% over a 24-hour period. Pretreatment with nicotinamide (12.5 mM) prevented anoxic and NO cytodegeneration by significantly increasing survival and decreasing membrane PS expression. Protection by nicotinamide in both neurons and ECs appeared to be independent and downstream from p38 activation. Further investigations that define the cellular and molecular mechanisms employed by the nutrient nicotinamide may provide greater insight into the potential therapeutic targets that determine neuronal and vascular injury.
authors.affiliation: Division of Cellular and Molecular Cerebral Ischemia, Center for Molecular Medicine and Genetics, Center for Molecular and Cellular Toxicology, Wayne State University School of Medicine, Detroit, MI 48201.
authors.forename: Shi-Hua
authors.initials: SH
authors.lastname: Lin
authors.forename: Zhao Zhong
authors.initials: ZZ
authors.lastname: Chong
authors.forename: Kenneth
authors.initials: K
authors.lastname: Maiese