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Brain Res. 2014 Jan 16;1543:28-37. doi: 10.1016/j.brainres.2013.11.018. Epub 2013 Nov 23.

Expression of the CHOP-inducible carbonic anhydrase CAVI-b is required for BDNF-mediated protection from hypoxia.

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Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
Undergraduate Program in Neuroscience, University of Rochester, Rochester, NY, USA.
Undergraduate Program in Cell and Developmental Biology, University of Rochester, Rochester, NY, USA.
Institute of Biomedical Technology and School of Medicine, University of Tampere, Tampere, Finland.
Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA.
Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA; Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY, USA. Electronic address:


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.


Brain-derived neurotrophic factor (BDNF); Carbonic anhydrase; Ischemia; Neurosphere; Oxygen glucose deprivation (OGD); Unfolded protein response (UPR)

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