Nuclear and extranuclear effects of vitamin A

Abstract

Vitamin A or retinol is a multifunctional vitamin that is essential at all stages of life from embryogenesis to adulthood. Up to now, it has been accepted that the effects of vitamin A are exerted by active metabolites, the major ones being 11-cis retinal for vision, and all trans-retinoic acid (RA) for cell growth and differentiation. Basically RA binds nuclear receptors, RARs, which regulate the expression of a battery of target genes in a ligand dependent manner. During the last decade, new scenarios have been discovered, providing a rationale for the understanding of other long-noted but not explained functions of retinol. These novel scenarios involve: (i) other nuclear receptors such as PPAR β/δ, which regulate the expression of other target genes with other functions; (ii) extranuclear and nontranscriptional effects, such as the activation of kinases, which phosphorylate RARs and other transcription factors, thus expanding the list of the RA-activated genes; (iii) finally, vitamin A is active per se and can work as a cytokine that regulates gene transcription by activating STRA6. New effects of vitamin A and RA are continuously being discovered in new fields, revealing new targets and new mechanisms thus improving the understanding the pleiotropicity of their effects.