PUBLICATION

Ethanol-Induced ADH Activity in Zebrafish: Differential Concentration-Dependent Effects on High- Versus Low-Affinity ADH Enzymes

Authors
Tran, S., Nowicki, M., Facciol, A., Chatterjee, D., Gerlai, R.
ID
ZDB-PUB-160108-1
Date
2016
Source
Zebrafish   13(2): 75-8 (Journal)
Registered Authors
Gerlai, Robert T.
Keywords
none
MeSH Terms
  • Alcohol Dehydrogenase/analysis
  • Alcohol Dehydrogenase/metabolism*
  • Animals
  • Dose-Response Relationship, Drug
  • Enzyme Activation/drug effects
  • Ethanol/pharmacology*
  • Female
  • Isoenzymes/analysis
  • Isoenzymes/metabolism
  • Liver/drug effects*
  • Liver/enzymology*
  • Male
  • Zebrafish/metabolism*
PubMed
26741829 Full text @ Zebrafish
Abstract
Zebrafish express enzymes that metabolize ethanol in a manner comparable to that of mammals, including humans. We previously demonstrated that acute ethanol exposure increases alcohol dehydrogenase (ADH) activity in an inverted U-shaped dose-dependent manner. It was hypothesized that the biphasic dose-response was due to the increased activity of a high-affinity ADH isoform following exposure to low concentrations of ethanol and increased activity of a low-affinity ADH isoform following exposure to higher concentrations of ethanol. To test this hypothesis, we exposed zebrafish to different concentrations of ethanol (0%, 0.25%, 0.5%, and 1.0% v/v) for 30 min and measured the total ADH activity in the zebrafish liver. However, we also repeated this enzyme activity assay using a low concentration of the substrate (ethanol) to determine the activity of high-affinity ADH isoforms. We found that total ADH activity in response to ethanol induces an inverted U-shaped dose-response similar to our previous study. Using a lower substrate level in our enzyme assay targeting high-affinity isozymes, we found a similar dose-response. However, the difference in activity between the high and low substrate assays (high substrate activity - low substrate activity), which provide an index of activity for low-affinity ADH isoforms, revealed no significant effect of ethanol exposure. Our results suggest that the inverted U-shaped dose-response for total ADH activity in response to ethanol is driven primarily by high-affinity isoforms of ADH.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping