Expression of the CHOP-inducible carbonic anhydrase CAVI-b is required for BDNF-mediated protection from hypoxia.
Brain Res
; 1543: 28-37, 2014 Jan 16.
Article
en En
| MEDLINE
| ID: mdl-24275196
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Hipoxia de la Célula
/
Regulación de la Expresión Génica
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Anhidrasas Carbónicas
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Factor Neurotrófico Derivado del Encéfalo
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Factor de Transcripción CHOP
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Brain Res
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos