Pre–B-Cell Colony–Enhancing Factor Regulates NAD + -Dependent Protein Deacetylase Activity and Promotes Vascular Smooth Muscle Cell Maturation
| Autor: | Zengxuan Nong, Caroline O'Neil, J. Geoffrey Pickering, Eric van der Veer, Brad L. Urquhart, David J. Freeman |
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| Rok vydání: | 2005 |
| Předmět: |
Vascular smooth muscle
Cell Survival Physiology Myocytes Smooth Muscle Nicotinamide phosphoribosyltransferase activity Nicotinamide phosphoribosyltransferase Neovascularization Physiologic Apoptosis Biology Cell Maturation Muscle Smooth Vascular chemistry.chemical_compound Downregulation and upregulation Humans Sirtuins Myocyte Pentosyltransferases RNA Small Interfering Nicotinamide Phosphoribosyltransferase Cells Cultured Protein deacetylase activity NAD musculoskeletal system Up-Regulation Cell biology Biochemistry chemistry cardiovascular system Cytokines NAD+ kinase Cardiology and Cardiovascular Medicine Oxidation-Reduction tissues |
| Zdroj: | Circulation Research. 97:25-34 |
| ISSN: | 1524-4571 0009-7330 |
| DOI: | 10.1161/01.res.0000173298.38808.27 |
| Popis: | Conversion of vascular smooth muscle cells (SMCs) from a proliferative state to a nonproliferative, contractile state confers vasomotor function to developing and remodeling blood vessels. Using a maturation-competent human SMC line, we determined that this shift in phenotype was accompanied by upregulation of pre–B-cell colony–enhancing factor (PBEF), a protein proposed to be a cytokine. Knockdown of endogenous PBEF increased SMC apoptosis and reduced the capacity of synthetic SMCs to mature to a contractile state. In keeping with these findings, human SMCs transduced with the PBEF gene had enhanced survival, an elongated bipolar morphology, and increased levels of h-caldesmon, smoothelin-A, smoothelin-B, and metavinculin. Notwithstanding some prior reports, PBEF did not have attributes of a cytokine but instead imparted the cell with increased nicotinamide phosphoribosyltransferase activity. Intracellular nicotinamide adenine dinucleotide (NAD + ) content was increased in PBEF-overexpressing SMCs and decreased in PBEF-knockdown SMCs. Furthermore, NAD + -dependent protein deacetylase activity was found to be essential for SMC maturation and was increased by PBEF. Xenotransplantation of human SMCs into immunodeficient mice revealed an increased capacity for PBEF-overexpressing SMCs to mature and intimately invest nascent endothelial channels. This microvessel chimerism and maturation process was perturbed when SMC PBEF expression was lowered. These findings identify PBEF as a regulator of NAD + -dependent reactions in SMCs, reactions that promote, among other potential processes, the acquisition of a mature SMC phenotype. |
| Databáze: | OpenAIRE |
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