PUBLICATION

Roles of carbonic anhydrase 8 in neuronal cells and zebrafish

Authors
Huang, M.S., Wang, T.K., Liu, Y.W., Li, Y.T., Chi, T.H., Chou, C.W., Hsieh, M.
ID
ZDB-PUB-140513-42
Date
2014
Source
Biochimica et biophysica acta. General subjects   1840(9): 2829-2842 (Journal)
Registered Authors
Liu, Yi-wen
Keywords
Carbonic anhydrase 8, Cell migration and invasion, Cerebellar granule neuron, Neuro-2a, SK-N-SH, Zebrafish
MeSH Terms
  • Animals
  • Biomarkers, Tumor/biosynthesis*
  • Biomarkers, Tumor/genetics
  • Cell Line
  • Cerebellum/enzymology*
  • Cerebellum/pathology
  • Disease Models, Animal
  • Gene Knockdown Techniques
  • Humans
  • Mice
  • Mice, Inbred ICR
  • Nerve Tissue Proteins/biosynthesis*
  • Nerve Tissue Proteins/genetics
  • Nervous System Diseases/enzymology*
  • Nervous System Diseases/genetics
  • Nervous System Diseases/pathology
  • Neurons/enzymology*
  • Neurons/pathology
  • Zebrafish
  • Zebrafish Proteins/biosynthesis*
  • Zebrafish Proteins/genetics
PubMed
24794067 Full text @ BBA General Subjects
Abstract
Carbonic anhydrase 8 (CA8) is an isozyme of α-carbonic anhydrases (CAs). Previous studies showed that CA8 can be detected in human adult brain, with more intense expression in the cerebellum. Single mutations in CA8 were reported to cause novel syndromes like ataxia, mild mental retardation or the predisposition to quadrupedal gait.
In the present study, we examine the functions of CA8 in neuronal cell lines, mouse cerebellar granule neurons and zebrafish.
We demonstrated that overexpression of CA8 in neuronal cells significantly decreased cell death under staurosporine treatment. Moreover, CA8 overexpression significantly increased cell migration and invasion ability in neuronal cells and in mouse cerebellar granule neurons, implicating that CA8 may be involved in neuron motility and oncogenesis. By using zebrafish as an animal model, motor reflection of 3dpf zebrafish embryos was significantly affected after the down-regulation of CA8 through ca8 morpholino.
We concluded that CA8 overexpression desensitizes neuronal cells to STS induced apoptotic stress and increases cell migration and invasion ability in neuronal cells. In addition, down-regulated CA8 decreases neuron mobility in neuronal cells and leads to abnormal calcium release in cerebellar granule neurons. Knockdown of the ca8 gene results in an abnormal movement pattern in zebrafish.
Our findings provide evidence to support that the impaired protective function of CA8 contributes to human neuropathology, and to suggest that zebrafish can be used as an animal model to study the biological functions of human CA8 in vivo.
Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping