Ethanol inhibition of retinoic acid synthesis as a potential mechanism for fetal alcohol syndrome

@article{Deltour1996EthanolIO,
  title={Ethanol inhibition of retinoic acid synthesis as a potential mechanism for fetal alcohol syndrome},
  author={L. Deltour and H. Ang and G. Duester},
  journal={The FASEB Journal},
  year={1996},
  volume={10},
  pages={1050 - 1057}
}
Retinoic acid (RA) is known to act as a signaling molecule during embryonic development, but little is known about the regulation of RA synthesis from retinol. The rate‐limiting step in RA synthesis is the oxidation of retinol, a reaction that can be catalyzed by alcohol dehydrogenase (ADH). Ethanol is also a substrate for ADH, and high levels of ethanol inhibit ADH‐catalyzed retinol oxidation. This has prompted us to hypothesize that ethanol‐induced defects observed in fetal alcohol syndrome… Expand
Acetaldehyde inhibits retinoic acid biosynthesis to mediate alcohol teratogenicity
TLDR
It is concluded that acetaldehyde is the teratogenic derivative of ethanol responsible for the reduction in RA signaling and induction of the developmental malformations characteristic of FASD. Expand
Competition between ethanol clearance and retinoic acid biosynthesis in the induction of fetal alcohol syndrome.
TLDR
All of the evidence supports the reduction of retinoic acid signaling as the etiological trigger in the induction of FASD. Expand
Stimulation of retinoic acid production and growth by ubiquitously expressed alcohol dehydrogenase Adh3
TLDR
There is genetic evidence that alcohol dehydrogenase (ADH) performs this function by demonstrating a role for Adh3, a ubiquitously expressed form, and ADH3 was also shown to have in vitro retinol oxidation activity. Expand
Alcohol dehydrogenase as a critical mediator of retinoic acid synthesis from vitamin A in the mouse embryo.
  • G. Duester
  • Biology, Medicine
  • The Journal of nutrition
  • 1998
TLDR
Findings suggest that ADH-IV participates in the initiation of retinoid signaling by functioning as a retinol dehydrogenase and that this can be inhibited by ethanol intoxication. Expand
Ethanol increases retinoic acid production in cerebellar astrocytes and in cerebellum.
TLDR
It was found that astrocytes are the predominant source of postnatal RA synthesis in the cerebellum, and a mechanism by which ethanol could stimulate RA synthesis is via the ethanol-activated short-chain retinol dehydrogenases, which are shown to be present in the postnatal Cerebellum. Expand
The role of retinoid metabolism by alcohol and aldehyde dehydrogenases in differentiation of cultured neuronal cells.
TLDR
C cultured neuronal cells could be used a model system in which to study the effects of ethanol and acetaldehyde on retinoid- regulated neuronal cell differentiation, and a human neuroblastoma cell line, SH-SY5Y, was chosen because it had previously been shown to be responsive to retinoic acid. Expand
The interaction of ethanol and vitamin A as a potential mechanism for the pathogenesis of Fetal Alcohol syndrome.
TLDR
This review summarizes recent research on the interaction of ethanol and vitamin A in models that explore if an interaction between these two compounds might potentially be the mechanism for fetal alcohol syndrome. Expand
Effects of ethanol on physiological retinoic acid levels
TLDR
No robust data support inhibition of vitamin A metabolism, resulting in decreased atRA in vivo during normal vitamin A nutriture, and insight into whether interactions between ethanol and retinoids represent cause versus effect requires additional research. Expand
Retinol/Ethanol Drug Interaction during Acute Alcohol Intoxication in Mice Involves Inhibition of Retinol Metabolism to Retinoic Acid by Alcohol Dehydrogenase*
TLDR
The findings demonstrate that the reduced RA levels observed during acute retinol/ethanol drug interaction are due primarily to a decrease in ADH-catalyzed RA synthesis and secondarily to an increase in RA degradation. Expand
Ethanol induces embryonic malformations by competing for retinaldehyde dehydrogenase activity during vertebrate gastrulation
TLDR
The biochemical evidence shows that, at the onset of RA signaling during early gastrulation, the ethanol effect centers on the competition for the available retinaldehyde dehydrogenase activity. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 52 REFERENCES
A hypothetical mechanism for fetal alcohol syndrome involving ethanol inhibition of retinoic acid synthesis at the alcohol dehydrogenase step.
  • G. Duester
  • Biology, Medicine
  • Alcoholism, clinical and experimental research
  • 1991
TLDR
An hypothesis is presented in which many of the abnormalities observed in fetal alcohol syndrome may be caused by high levels of ethanol acting as a competitive inhibitor of ADH-catalyzed retinol oxidation in the embryo or fetus. Expand
Catalytic efficiency of human alcohol dehydrogenases for retinol oxidation and retinal reduction.
TLDR
The relative efficiency (V/Km) of eight human ADH isoenzymes for oxidation of all-trans-retinol and reduction of three retinal isomers are reported, and alpha alpha has the highest efficiency of all tested isoenZymes for 13-cis-retinal. Expand
Terminal-group oxidation of retinol by mouse epidermis. Inhibition in vitro and in vivo.
TLDR
The ability to inhibit the oxidation ofretinol to retinoic acid in mouse epidermis provides a potential method to resolve the roles of retinol and retinoIC acid in epithelial function. Expand
Mechanisms of ethanol-drug-nutrition interactions.
  • C. Lieber
  • Chemistry, Medicine
  • Journal of toxicology. Clinical toxicology
  • 1994
TLDR
A better understanding of the pathology induced by ethanol has now generated improved prospects for therapy, and the contribution of gastric alcohol dehydrogenase to the first pass metabolism of ethanol and alcohol-drug interactions is now recognized. Expand
Retinoic acid and craniofacial development: Molecules and morphogenesis
  • G. Morriss-Kay
  • Biology, Medicine
  • BioEssays : news and reviews in molecular, cellular and developmental biology
  • 1993
TLDR
This article proposes that the amount of RA reaching the nucleus in different embryonic tissues is modulated by a mechanism involving three cytoplasmic binding proteins for retinol (CRBP I) and retinoic acid (CRABP I and II). Expand
Retinol forms retinoic acid via retinal.
TLDR
The results of this study indicate that retinal is an obligatory intermediate in the hepatic production of retinoic acid fromretinol and that cytosolic and microsomal retinol dehydrogenases play a key role in this process. Expand
The inhibitory effect of ethanol on retinol oxidation by human liver and cattle retina.
  • E. Mezey, P. Holt
  • Chemistry, Medicine
  • Experimental and molecular pathology
  • 1971
TLDR
It is suggested that both ethanol and retinol are oxidized by the same enzyme in the liver, but not in the retina. Expand
Cloning of the Mouse Class IV Alcohol Dehydrogenase (Retinol Dehydrogenase) cDNA and Tissue-specific Expression Patterns of the Murine ADH Gene Family (*)
TLDR
The results presented here indicate that the mouse has a simpler ADH gene family than the human but has conserved class IV ADH previously shown to be a very active retinol dehydrogenase in humans. Expand
Stage-dependent effects of ethanol on cranial neural crest cell development: partial basis for the phenotypic variations observed in fetal alcohol syndrome.
TLDR
It is concluded that ethanol exposure seems to affect specific events adversely during neural crest development, and there are distinct developmental windows during which the CNCCs may be particularly susceptible to ethanol-induced cell death. Expand
Induction of normal cardiovascular development in the vitamin A-deprived quail embryo by natural retinoids.
TLDR
The studies suggest that there is a critical time point within the first 22-28 hr of quail embryogenesis when all-trans-retinoic acid initiates events that lead to normal cardiovascular development in the avian embryo. Expand
...
1
2
3
4
5
...