Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, USA.
J Cereb Blood Flow Metab. 2010 Dec;30(12):1962-71. doi: 10.1038/jcbfm.2010.71. Epub 2010 May 19.
Pre-B-cell colony-enhancing factor (PBEF) (also known as nicotinamide phosphoribosyltransferase) is a rate-limiting enzyme in the salvage pathway for mammalian biosynthesis of nicotinamide adenine dinucleotide (NAD(+)). By synthesizing NAD(+), PBEF functions to maintain an energy supply that has critical roles in cell survival. Cerebral ischemia is a major neural disorder with a high percentage of mortality and disability. Ischemia leads to energy depletion and eventually neuronal death and brain damage. This study investigated the role of PBEF in cerebral ischemia using a photothrombosis mouse model. Using immunostaining, we initially determined that PBEF is highly expressed in neurons, but not in glial cells in the mouse brain. To study the role of PBEF in ischemia in vivo, we used PBEF knockout heterozygous (Pbef+/-) mice. We showed that these mice have lower PBEF expression and NAD(+) level than do wild-type (WT) mice. When subjected to photothrombosis, Pbef+/- mice have significantly larger infarct volume than do age-matched WT mice at 24 hours after ischemia. Higher density of degenerating neurons was detected in the penumbra of Pbef+/- mice than in WT mice using Fluoro-Jade B staining. Our study shows that PBEF has a neuronal protective role in cerebral ischemia presumably through enhanced energy metabolism.
前期 B 细胞集落增强因子（PBEF）（也称为烟酰胺磷酸核糖基转移酶）是哺乳动物生物合成烟酰胺腺嘌呤二核苷酸（NAD(+))补救途径中的限速酶。通过合成 NAD(+)，PBEF 起到维持能量供应的作用，而能量供应在细胞存活中起着关键作用。脑缺血是一种主要的神经紊乱疾病，其死亡率和残疾率很高。缺血导致能量耗竭，最终导致神经元死亡和脑损伤。本研究使用光血栓形成小鼠模型研究了 PBEF 在脑缺血中的作用。通过免疫染色，我们最初确定 PBEF 在小鼠大脑中的神经元中高度表达，但不在神经胶质细胞中表达。为了研究 PBEF 在体内缺血中的作用，我们使用了 PBEF 敲除杂合子（Pbef+/-）小鼠。结果表明，与野生型（WT）小鼠相比，这些小鼠的 PBEF 表达和 NAD(+)水平较低。在光血栓形成后 24 小时，Pbef+/- 小鼠的梗死体积明显大于年龄匹配的 WT 小鼠。使用 Fluoro-Jade B 染色检测到 Pbef+/- 小鼠的半影区中退化神经元的密度高于 WT 小鼠。我们的研究表明，PBEF 在脑缺血中具有神经元保护作用，可能是通过增强能量代谢实现的。
