title: CPEB1 modulates lipopolysaccharide-mediated iNOS induction in rat primary astrocytes.
abstract: Upon CNS damage, astrocytes undergo a series of biological changes including increased proliferation, production of inflammatory mediators and morphological changes, in a response collectively called reactive gliosis. This process is an essential part of the brains response to injury, yet much is unknown about the molecular mechanism(s) that induce these changes. In this study, we investigated the role of cytoplasmic polyadenylation element binding protein 1 (CPEB1) in the regulation of inflammatory responses in a model of reactive gliosis, lipopolysaccharide-stimulated astrocytes. CPEB1 is an mRNA-binding protein recently shown to be expressed in astrocytes that may play a role in astrocytes migration. After LPS stimulation, the expression and phosphorylation of CPEB1 was increased in rat primary astrocytes in a JNK-dependent process. siRNA-induced knockdown of CPEB1 expression inhibited the LPS-induced up-regulation of iNOS as well as NO and ROS production, a hallmark of immunological activation of astrocytes. The results from the study suggest that CPEB1 is actively involved in the regulation of inflammatory responses in astrocytes, which might provide new insights into the regulatory mechanism after brain injury.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Seoul National University, Seoul, South Korea.
authors.forename: Ki Chan
authors.initials: KC
authors.lastname: Kim
authors.forename: So
authors.initials: S
authors.lastname: Hyun Joo
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Shin
mesh_terms: D000818:Animals; D001253:Astrocytes; D001930:Brain Injuries / Q000378:metabolism*; D015536:Down-Regulation; D004660:Encephalitis / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D008070:Lipopolysaccharides; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D018384:Oxidative Stress; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C539243:CPEB1 protein, rat; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D048670:MAP Kinase Kinase 4