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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.

Author information

  • 1Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
  • 2Undergraduate Program in Neuroscience, University of Rochester, Rochester, NY, USA.
  • 3Undergraduate Program in Cell and Developmental Biology, University of Rochester, Rochester, NY, USA.
  • 4Institute of Biomedical Technology and School of Medicine, University of Tampere, Tampere, Finland.
  • 5Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA.
  • 6Department 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: keith_nehrke@urmc.rochester.edu.

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.

© 2013 Published by Elsevier B.V.

KEYWORDS:

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

PMID:
24275196
[PubMed - indexed for MEDLINE]
PMCID:
PMC3888505
Free PMC Article
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