PMID- 9560303
OWN - NLM
STAT- MEDLINE
DCOM- 19981026
LR  - 20231213
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 331 ( Pt 3)
IP  - Pt 3
DP  - 1998 May 1
TI  - Inhibition of activation-induced apoptosis of thymocytes by all-trans- and 
      9-cis-retinoic acid is mediated via retinoic acid receptor alpha.
PG  - 767-74
AB  - Thymocytes can be induced to undergo apoptotic cell death by activation through 
      the T-cell receptor (TCR). This process requires macromolecular synthesis and has 
      been shown to be inhibited by retinoic acids (RAs). Two groups of nuclear 
      receptors for RAs have been identified: retinoic acid receptors (RARs) and 
      retinoid X receptors (RXRs). All-trans-RA is the high-affinity ligand for RARs, 
      and 9-cis-RA additionally binds to RXRs with high affinity. Because 9-cis-RA is 
      much more potent in inhibiting TCR-mediated death than all-trans-RA, it was 
      suggested that RXRs participate in the process. In the present study various 
      synthetic retinoid analogues were used to address this question further. The 
      results presented suggest that the inhibitory effect of RAs on activation-induced 
      death of thymocytes is mediated via RARalpha, because (1) it can be reproduced by 
      various RARalpha analogues both in vitro and in vivo, (2) the effect of RAs can 
      be inhibited by the addition of an RARalpha antagonist, (3) CD4+CD8+thymocytes, 
      which die on TCR stimulation, express RARalpha. Stimulation of RARgamma, in 
      contrast, enhances the activation-induced death of thymocytes and inhibits its 
      prevention by RARalpha stimulation. RXR co-stimulation suspends this inhibitory 
      effect of RARgamma and permits the preventive function of RARalpha on 
      activation-induced death. Our results suggest a complex interaction between the 
      various isoforms of retinoid receptors and demonstrate that low (physiological) 
      concentrations of all-trans-RA do not affect the activation-induced death of 
      thymocytes because the RARalpha-mediated inhibitory and the RARgamma-mediated 
      enhancing pathways are in balance, whereas if 9-cis-RA is formed, additional 
      stimulation of RXRs permits the inhibitory action of RARalpha.
FAU - Szondy, Z
AU  - Szondy Z
AD  - Department of Biochemistry, University Medical School of Debrecen, H-4012 
      Debrecen, Hungary. szondy@indi.dote.hu
FAU - Reichert, U
AU  - Reichert U
FAU - Bernardon, J M
AU  - Bernardon JM
FAU - Michel, S
AU  - Michel S
FAU - Toth, R
AU  - Toth R
FAU - Karaszi, E
AU  - Karaszi E
FAU - Fesus, L
AU  - Fesus L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Antibodies)
RN  - 0 (Antigens, CD)
RN  - 0 (Benzoates)
RN  - 0 (Rara protein, mouse)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoic Acid Receptor alpha)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinoids)
RN  - 0 (Tetrahydronaphthalenes)
RN  - 0 (Transcription Factors)
RN  - 102121-60-8 (Am 580)
RN  - 1UA8E65KDZ (Alitretinoin)
RN  - 37558-16-0 (Phorbol 12,13-Dibutyrate)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Alitretinoin
MH  - Animals
MH  - Antibodies/immunology/pharmacology
MH  - Antigens, CD/immunology
MH  - Apoptosis/*drug effects
MH  - Benzoates/pharmacology
MH  - Cells, Cultured
MH  - DNA Fragmentation/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Phorbol 12,13-Dibutyrate/pharmacology
MH  - Protein Binding/physiology
MH  - Receptors, Antigen, T-Cell/physiology
MH  - Receptors, Retinoic Acid/metabolism/*physiology
MH  - Retinoic Acid Receptor alpha
MH  - Retinoid X Receptors
MH  - Retinoids/pharmacology
MH  - Tetrahydronaphthalenes/pharmacology
MH  - Thymus Gland/*drug effects
MH  - Transcription Factors/physiology
MH  - Tretinoin/*pharmacology
MH  - Retinoic Acid Receptor gamma
PMC - PMC1219416
EDAT- 1998/04/30 00:00
MHDA- 1998/04/30 00:01
PMCR- 1998/11/01
CRDT- 1998/04/30 00:00
PHST- 1998/04/30 00:00 [pubmed]
PHST- 1998/04/30 00:01 [medline]
PHST- 1998/04/30 00:00 [entrez]
PHST- 1998/11/01 00:00 [pmc-release]
AID - 10.1042/bj3310767 [doi]
PST - ppublish
SO  - Biochem J. 1998 May 1;331 ( Pt 3)(Pt 3):767-74. doi: 10.1042/bj3310767.