Abstract
Retinoic acid is a morphogen that plays important roles during fetal growth in specification of head and limb bud development (Hofman and Eichele, 1994), and probably also in regulation of neuronal development (Holder and Maden, 1992). Exposure of the developing fetus to ethanol can cause a range of deformities and neurological abnormalities, leading to conditions known in humans as fetal alcohol syndrome (FAS) and alcohol related neurodevelopmental disorder (ARND) (Sampson et al., 1997). Retinoic acid is formed from retinol (vitamin A) via oxidation first to retinal, catalysed by isozymes of alcohol dehydrogenase (ADH) or the short chain dehydrogenase/reductase family. Retinal is then oxidised to retinoic acid by aldehyde dehydrogenase (A1DH), retinal dehydrogenase or microsomal cytochrome P450 1A1 or 1A2 (Duester, 1996). Retinoic acid has its effect on fetal development through binding to nuclear receptors and forming transcription factors which n regulate gene expression (De Luca, 1991; Chambon, 1996). It has been postulated that one of the mechanisms leading to the development of FAS or ARND may be inhibition of retinoic acid production caused by competitive inhibition of alcohol and/or aldehyde dehydrogenases during ethanol metabolism (Duester, 1991, Deltour et al., 1996). e present study was initiated to see whether 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. A human neuroblastoma cell line, SH-SY5Y, was chosen because it had previously been shown to be responsive to retinoic acid (Pahlman et al., 1984).
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call