Retinoic Acid Attenuates Cell Death and Reduces Tyrosine Hydroxylase Expression in Ethanol-Treated Human SH-SY5Y Neuroblastoma Cells

Abstract

Background: Retinoic acid (RA) plays an important role in embryonic development and central nervous system function, and has been shown to exert anti-apoptotic effects in various cells. In contrast, ethanol probably exerts its toxicity via pro-apoptotic effects. Here, we investigated the effects of all-trans RA on ethanol-induced cell death in human dopaminergic SH-SY5Y neuroblastoma cells.

Methods: Cell viability of SH-SY5Y cells exposed to 25, 50, 100, and 200 mM ethanol for 72 hours, with or without 10 µM RA, was measured using an MTT assay. Expression of p53, Bcl, and Bax mRNA levels in untreated SH-SY5Y cells and cells exposed to 200 mM ethanol, 10 µM RA, or both for 24 hours was analyzed using quantitative real-time RT-PCR. Tyrosine hydroxylase (TH) of SH-SY5Y cells exposed to 25, 50, 100, and 200 mM ethanol for 72 hours, with or without 10 µM RA, was measured using western blotting analysis.

Results: The effect of ethanol on cell viability was dose-dependent, and was accompanied by the significant reduction of p53 and Bax mRNA expression, including Bax/Bcl-2 ratio. Western blotting analysis showed that 72 hours of treatment with 200 mM ethanol significantly increased TH expression, but the expression was significantly decreased when cells were co-cultured with 10 µM RA and 200 mM ethanol.

Conclusions: All-trans RA could protect against apoptosis via a p53-dependent pathway and reduce the biochemical adaptation of ethanol-treated SH-SY5Y cells.




J Neurol Res. 2012;2(5):204-210
doi: https://doi.org/10.4021/jnr147w