In the last years there has been an increasing interest in the role of RXR, especially RXRα in alcoholic liver disease. Accumulating evidence suggests that RXR may play a major role in many aspects of ethanol metabolism being its expression downregulated by ethanol [42, 97]. In fact, mice fed with ethanol show reduced ability of PPAR/RXR heterodimers to bind DNA and reduced RXR expression [29]. These effects are acetaldehyde dependent because blocking ADH reduces, while blocking ADLH increases, the observed phenotype [28]. Moreover, the human aldehyde dehydrogenase-2 promoter contains a retinoid response element (designated FP330-3′), which may contribute to the regulation of the gene. Heterodimers of retinoic acid receptor (RAR)α, β, and γ with RXRα bound the FP330-3′ site, stimulating the expression of reporter constructs containing the FP330-3′ sites in a 9-cis retinoic acid-dependent fashion in cultured cells.
