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
In vertebrates, both nuclear all-trans and 9-cis retinoic acid receptors (RAR and RXR) belonging to the steroid/thyroid/retinoid nuclear receptor superfamily play a crucial role in the vitamin A action. Qualitative analysis of all known RAR or RXR subtypes in both pooled and non-pooled peripheral blood mononuclear cells (PBMC) from healthy human subjects has been performed by reverse transcription and polymerase chain reaction (RT-PCR). Our data, based on qualitative RT-PCR analysis has shown that human PBMC are capable to express RAR alpha, RAR gamma, RXR alpha, and RXR beta.
Subject(s)
Cell Nucleus/metabolism , Leukocytes, Mononuclear/metabolism , Receptors, Retinoic Acid/metabolism , Cell Nucleus/genetics , DNA Primers/chemistry , Electrophoresis, Agar Gel , Humans , RNA, Messenger/metabolism , Receptors, Retinoic Acid/classification , Receptors, Retinoic Acid/genetics , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Transglutaminases catalyze the posttranslation modification of proteins by catalyzing Ca2+ dependent acyl-transfer reaction resulting in the formation of new g-amide bonds between g-carboxamide groups of peptide-bound glutamine residues and various primary amines. Such glutamine residue serves as acyl-donor and the most common acyl-acceptors are e-amino groups of peptide-bound lysine residues or primary amino groups of some naturally occurring polyamines, like putrescine or spermidine. The active site of cysteine reacts first with the g-carboxamide group of glutamine residue to form the acyl-enzyme intermediate under the release of ammonia. In the second step, the complex reacts with a primary amine to form an isopeptide bond and liberate the reactivated enzyme. The presence of transglutaminases has been observed in various endocrine glands such as human pituitary, which was investigated by immunohistochemical methods using specific antibodies. A significant increase in the expression and activity of tissue transglutaminase was observed during involution of thymus. In the genital tract of the male rat two different forms of the enzyme transglutaminase could be identified and characterized. the presence of p53 and tissues transglutaminase gene expressions in human normal and pathologic adrenal tissues. The Ca2+-responsive enzyme transglutaminase, which catalyzes the cross-bridging of proteins, was found in pancreatic islet cells.
Subject(s)
Endocrine Glands/enzymology , Transglutaminases/metabolism , Animals , Binding Sites , Cysteine/metabolism , Humans , Protein Processing, Post-Translational , Tissue Distribution , Transglutaminases/analysisABSTRACT
In the present work the role of 13-cis retinoic acid and CpG oligodeoxynucleotides (CpG-ODN) in a 1-methyl-1-nitrosourea (MNU)-induced mammary gland carcinoma animal model was investigated. Treatment with both components, applied either alone or in combination, induced a significant decrease of the tumour burden and the volume of tumours only in rats that received CpG-ODN (p = 0.046, compared to the MNU control group). The data indicate that the Th-1 biased immunostimulatory capacities of CpG motifs may play a significant role in induction of protective immune responses against mammary gland tumours in Sprague-Dawley rats.
