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
Citation
Tran, S., Nowicki, M., Facciol, A., Chatterjee, D., Gerlai, R. (2016) Ethanol-Induced ADH Activity in Zebrafish: Differential Concentration-Dependent Effects on High- Versus Low-Affinity ADH Enzymes. Zebrafish. 13(2):75-8.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping