Neuronal Protective Role of PBEF in a Mouse Model of Cerebral Ischemia
Open Access
- 19 May 2010
- journal article
- Published by SAGE Publications in Journal of Cerebral Blood Flow & Metabolism
- Vol. 30 (12), 1962-1971
- https://doi.org/10.1038/jcbfm.2010.71
Abstract
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.Keywords
This publication has 39 references indexed in Scilit:
- Nampt: linking NAD biology, metabolism and cancerTrends in Endocrinology & Metabolism, 2009
- The NAD World: A New Systemic Regulatory Network for Metabolism and Aging—Sirt1, Systemic NAD Biosynthesis, and Their ImportanceCell Biochemistry and Biophysics, 2009
- Photothrombosis ischemia stimulates a sustained astrocytic Ca2+ signaling in vivoGlia, 2008
- Bioenergetics of cerebral ischemia: A cellular perspectiveNeuropharmacology, 2008
- Essential Role of Pre–B-Cell Colony Enhancing Factor in Ventilator-induced Lung InjuryAmerican Journal of Respiratory and Critical Care Medicine, 2008
- Enhanced Astrocytic Ca2+Signals Contribute to Neuronal Excitotoxicity after Status EpilepticusJournal of Neuroscience, 2007
- Pre–B cell colony‐enhancing factor/visfatin, a new marker of inflammation in rheumatoid arthritis with proinflammatory and matrix‐degrading activitiesArthritis & Rheumatism, 2007
- Circulating Levels of Visfatin/Pre–B-Cell Colony–Enhancing Factor 1 in Relation to Genotype, GFR, Body Composition, and Survival in Patients With CKDAmerican Journal of Kidney Diseases, 2007
- Use of a Poly(ADP-Ribose) Polymerase Inhibitor to Suppress Inflammation and Neuronal Death After Cerebral Ischemia-ReperfusionStroke, 2007
- Increased Nuclear NAD Biosynthesis and SIRT1 Activation Prevent Axonal DegenerationScience, 2004