ABSTRACT
The regulation of cell growth and differentiation and also expression of a number of genes by retinoids are mediated by nuclear retinoid receptors (RARs and/or RXRs). In this study we investigated age-related alteration in both RAR and RXR receptor subtypes gene expression and tissue transglutaminase (tTG) activity before and after supplementation with 13-cis retinoic acid (13cRA) in human peripheral blood mononuclear cells (PBMCs). Healthy men (40) were divided in two groups according to their age (young group: 26.1+/-4.1 years and old group: 65.4+/-3.8 years). Each volunteer received 13cRA (Curacné), 0.5mg/(kgday)) during a period of 4 weeks. We have shown that RXRbeta expression was decreased significantly (p=0.0108) in PBMCs of elderly men when compared to that of young volunteers. Distribution of retinoic acid receptor subtype expression in PBMCs was found in the order: RXRbeta>RARgamma>RXRalpha>RARalpha. The tTG activity in PBMCs reflected a trend to be enhanced after 13-cis retinoic acid supplementation. In conclusion, we demonstrate a significant decrease in the expression of RXRbeta subtype of rexinoid receptors in PBMCs of healthy elderly men. Our data suggest that in healthy elderly men reduction of RXRbeta expression in PBMCs might be a common feature of physiological senescence.
Subject(s)
Aging/genetics , Dietary Supplements , Isotretinoin/therapeutic use , Leukocytes, Mononuclear/drug effects , Retinoid X Receptor beta/genetics , Adult , Age Factors , Aged , Aging/blood , Alitretinoin , Cellular Senescence/drug effects , Cellular Senescence/genetics , Down-Regulation/drug effects , GTP-Binding Proteins , Humans , Isotretinoin/blood , Isotretinoin/pharmacology , Leukocytes, Mononuclear/enzymology , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Protein Glutamine gamma Glutamyltransferase 2 , RNA, Messenger/blood , Receptors, Retinoic Acid/genetics , Reference Values , Retinoic Acid Receptor alpha , Retinoid X Receptor alpha/genetics , Retinoid X Receptor beta/blood , Time Factors , Transglutaminases/blood , Tretinoin/blood , Retinoic Acid Receptor gammaABSTRACT
Vitamin D is considered multifunctional steroid hormone that modulates calcium homeostasis through actions predominantly in kidney, bone and the intestinal tract. Nuclear vitamin D receptor (VDR) is a specific nuclear protein, a member of steroid hormone receptor superfamily. The amino acid sequence of the VDR shows a significant homology with other members of the nuclear hormone receptor superfamily, including receptors for glucocorticoids (GR), oestrogen (ER), androgen (AR), progesteron (PR), thyroid hormone (T3R), retinoic acid (RAR), retinoid X (RXR) and over 150 orphan receptors. VDR is known to mediate the pleiotropic biological actions of 1a,25-dihydroxyvitamin D3 through its ability to modulate the expression of target genes. VDR upon binding 1a,25-dihydroxyvitamin D3 regulates specific gene transcription predominantly by binding as a heterodimer with the retinoid X receptor (RXR) to DNA enhancer sequence, termed the vitamin D-responsive element (VDRE) that is present within the promoter region of vitamin D-controlled genes. The VDR has been shown to associate with several additional molecules to form the active transcriptional complex required for gene regulation. The regulation of this ligand-activated cellular transcription factor occurs at both transcriptional and posttranslational levels. This article summarizes a variety of effects of 1a,25-dihydroxyvitamin D3, acting through its cognate nuclear receptor, and its use in chemotherapy and chemoprevention of cancer.
