Nicotinamide: A Nutritional Supplement that Provides Protection Against Neuronal and Vascular Injury.
Nicotinamide: A Nutritional Supplement that Provides Protection Against Neuronal and Vascular Injury.
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DOI：
10.1089/10966200152053686
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发表时间：
2001-01-01
影响因子：
2.4
通讯作者：
Maiese, Kenneth
中科院分区：
文献类型：
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作者：
Lin, Shi-Hua;Chong, Zhao Zhong;Maiese, Kenneth
除了作为细胞生长和维持的必需营养素外，烟酰胺也可能是一种有吸引力的治疗剂，其对自由基缺血性程序性细胞死亡（PCD）具有疗效。然而，介导细胞PCD的细胞机制以及烟酰胺的保护作用被认为需要进一步定义。在原代大鼠海马神经元和大鼠脑血管内皮细胞（EC），细胞损伤通过台盼蓝染料排斥，外化膜磷脂酰丝氨酸（PS）残基，并通过Western印迹分析丝裂原活化蛋白激酶p38的激活。在神经元和EC群体中，烟酰胺在低于50 mM的浓度下没有细胞毒性。暴露于缺氧或一氧化氮（NO）供体硝普钠和NOC-9显着降低神经元和EC的生存从约85%至38%，并增加膜PS暴露从约10%至80%，超过24小时。预处理与烟酰胺（12.5 mM）防止缺氧和NO细胞变性显着增加生存和降低膜PS表达。烟酰胺在神经元和内皮细胞中的保护作用似乎是独立的，并且是p38激活的下游。进一步研究确定营养素烟酰胺所采用的细胞和分子机制，可以更深入地了解决定神经元和血管损伤的潜在治疗靶点。
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.