Expression of the CHOP-inducible carbonic anhydrase CAVI-b is required for BDNF-mediated protection from hypoxia
| Autor: | Teresa A. Sherman, Peiwen Pan, Allyssa Abel, Seppo Parkkila, Tori A. Matthews, Marc W. Halterman, Chris Demme, Keith Nehrke |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Gene isoform
Cellular differentiation CHOP Article Mice Neural Stem Cells Mesencephalon Carbonic anhydrase Animals Protein Isoforms Molecular Biology Cells Cultured Carbonic Anhydrases Transcription Factor CHOP Regulation of gene expression Brain-derived neurotrophic factor Mice Knockout Analysis of Variance biology L-Lactate Dehydrogenase General Neuroscience Brain-Derived Neurotrophic Factor Cell Differentiation Embryo Mammalian Cell Hypoxia Mice Inbred C57BL Glucose Biochemistry Gene Expression Regulation biology.protein Neurology (clinical) Signal transduction Developmental Biology |
| Popis: | Carbonic anhydrases (CAs) comprise a family of zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide. CAs contribute to a myriad of physiological processes, including pH regulation, anion transport and water balance. To date, 16 known members of the mammalian alpha-CA family have been identified. Given that the catalytic family members share identical reaction chemistry, their physiologic roles are influenced greatly by their tissue and sub-cellular locations. CAVI is the lone secreted CA and exists in both saliva and the gastrointestinal mucosa. An alternative, stress-inducible isoform of CAVI (CAVI-b) has been shown to be expressed from a cryptic promoter that is activated by the CCAAT/Enhancer-Binding Protein Homologous Protein (CHOP). The CAVI-b isoform is not secreted and is currently of unknown physiological function. Here we use neuronal models, including a model derived using Car6 and CHOP gene ablations, to delineate a role for CAVI-b in ischemic protection. Our results demonstrate that CAVI-b expression, which is increased through CHOP-signaling in response to unfolded protein stress, is also increased by oxygen-glucose deprivation (OGD). While enforced expression of CAVI-b is not sufficient to protect against ischemia, CHOP regulation of CAVI-b is necessary for adaptive changes mediated by BDNF that reduce subsequent ischemic damage. These results suggest that CAVI-b comprises a necessary component of a larger adaptive signaling pathway downstream of CHOP. |
| Databáze: | OpenAIRE |
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