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Inhibition of activation-induced apoptosis of thymocytes by all-trans- and 9-cis-retinoic acid is mediated via retinoic acid receptor α
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| Zeitschriftentitel: | Biochemical Journal |
|---|---|
| Personen und Körperschaften: | , , , , , , |
| In: | Biochemical Journal, 331, 1998, 3, S. 767-774 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Portland Press Ltd.
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| Schlagwörter: |
| author_facet |
SZONDY, Zsuzsa REICHERT, Uwe BERNARDON, Jean-Michel MICHEL, Serge TÓTH, Réka KARÁSZI, Éva FÉSÜS, László SZONDY, Zsuzsa REICHERT, Uwe BERNARDON, Jean-Michel MICHEL, Serge TÓTH, Réka KARÁSZI, Éva FÉSÜS, László |
|---|---|
| author |
SZONDY, Zsuzsa REICHERT, Uwe BERNARDON, Jean-Michel MICHEL, Serge TÓTH, Réka KARÁSZI, Éva FÉSÜS, László |
| spellingShingle |
SZONDY, Zsuzsa REICHERT, Uwe BERNARDON, Jean-Michel MICHEL, Serge TÓTH, Réka KARÁSZI, Éva FÉSÜS, László Biochemical Journal Inhibition of activation-induced apoptosis of thymocytes by all-trans- and 9-cis-retinoic acid is mediated via retinoic acid receptor α Cell Biology Molecular Biology Biochemistry |
| author_sort |
szondy, zsuzsa |
| spelling |
SZONDY, Zsuzsa REICHERT, Uwe BERNARDON, Jean-Michel MICHEL, Serge TÓTH, Réka KARÁSZI, Éva FÉSÜS, László 0264-6021 1470-8728 Portland Press Ltd. Cell Biology Molecular Biology Biochemistry http://dx.doi.org/10.1042/bj3310767 <jats:p>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 RARα, because (1) it can be reproduced by various RARα analogues both in vitro and in vivo, (2) the effect of RAs can be inhibited by the addition of an RARα antagonist, (3) CD4+CD8+thymocytes, which die on TCR stimulation, express RARα. Stimulation of RARγ, in contrast, enhances the activation-induced death of thymocytes and inhibits its prevention by RARα stimulation. RXR co-stimulation suspends this inhibitory effect of RARγ and permits the preventive function of RARα 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 RARα-mediated inhibitory and the RARγ-mediated enhancing pathways are in balance, whereas if 9-cis-RA is formed, additional stimulation of RXRs permits the inhibitory action of RARα.</jats:p> Inhibition of activation-induced apoptosis of thymocytes by all-trans- and 9-cis-retinoic acid is mediated via retinoic acid receptor α Biochemical Journal |
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Portland Press Ltd., 1998 |
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1998 |
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49 |
| title |
Inhibition of activation-induced apoptosis of thymocytes by all-trans- and 9-cis-retinoic acid is mediated via retinoic acid receptor α |
| title_unstemmed |
Inhibition of activation-induced apoptosis of thymocytes by all-trans- and 9-cis-retinoic acid is mediated via retinoic acid receptor α |
| title_full |
Inhibition of activation-induced apoptosis of thymocytes by all-trans- and 9-cis-retinoic acid is mediated via retinoic acid receptor α |
| title_fullStr |
Inhibition of activation-induced apoptosis of thymocytes by all-trans- and 9-cis-retinoic acid is mediated via retinoic acid receptor α |
| title_full_unstemmed |
Inhibition of activation-induced apoptosis of thymocytes by all-trans- and 9-cis-retinoic acid is mediated via retinoic acid receptor α |
| title_short |
Inhibition of activation-induced apoptosis of thymocytes by all-trans- and 9-cis-retinoic acid is mediated via retinoic acid receptor α |
| title_sort |
inhibition of activation-induced apoptosis of thymocytes by all-trans- and 9-cis-retinoic acid is mediated via retinoic acid receptor α |
| topic |
Cell Biology Molecular Biology Biochemistry |
| url |
http://dx.doi.org/10.1042/bj3310767 |
| publishDate |
1998 |
| physical |
767-774 |
| description |
<jats:p>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 RARα, because (1) it can be reproduced by various RARα analogues both in vitro and in vivo, (2) the effect of RAs can be inhibited by the addition of an RARα antagonist, (3) CD4+CD8+thymocytes, which die on TCR stimulation, express RARα. Stimulation of RARγ, in contrast, enhances the activation-induced death of thymocytes and inhibits its prevention by RARα stimulation. RXR co-stimulation suspends this inhibitory effect of RARγ and permits the preventive function of RARα 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 RARα-mediated inhibitory and the RARγ-mediated enhancing pathways are in balance, whereas if 9-cis-RA is formed, additional stimulation of RXRs permits the inhibitory action of RARα.</jats:p> |
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| author | SZONDY, Zsuzsa, REICHERT, Uwe, BERNARDON, Jean-Michel, MICHEL, Serge, TÓTH, Réka, KARÁSZI, Éva, FÉSÜS, László |
| author_facet | SZONDY, Zsuzsa, REICHERT, Uwe, BERNARDON, Jean-Michel, MICHEL, Serge, TÓTH, Réka, KARÁSZI, Éva, FÉSÜS, László, SZONDY, Zsuzsa, REICHERT, Uwe, BERNARDON, Jean-Michel, MICHEL, Serge, TÓTH, Réka, KARÁSZI, Éva, FÉSÜS, László |
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| description | <jats:p>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 RARα, because (1) it can be reproduced by various RARα analogues both in vitro and in vivo, (2) the effect of RAs can be inhibited by the addition of an RARα antagonist, (3) CD4+CD8+thymocytes, which die on TCR stimulation, express RARα. Stimulation of RARγ, in contrast, enhances the activation-induced death of thymocytes and inhibits its prevention by RARα stimulation. RXR co-stimulation suspends this inhibitory effect of RARγ and permits the preventive function of RARα 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 RARα-mediated inhibitory and the RARγ-mediated enhancing pathways are in balance, whereas if 9-cis-RA is formed, additional stimulation of RXRs permits the inhibitory action of RARα.</jats:p> |
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| imprint | Portland Press Ltd., 1998 |
| imprint_str_mv | Portland Press Ltd., 1998 |
| institution | DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Zi4, DE-Gla1, DE-15, DE-Pl11, DE-Rs1, DE-14, DE-105, DE-Ch1, DE-L229 |
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| match_str | szondy1998inhibitionofactivationinducedapoptosisofthymocytesbyalltransand9cisretinoicacidismediatedviaretinoicacidreceptora |
| mega_collection | Portland Press Ltd. (CrossRef) |
| physical | 767-774 |
| publishDate | 1998 |
| publishDateSort | 1998 |
| publisher | Portland Press Ltd. |
| record_format | ai |
| recordtype | ai |
| series | Biochemical Journal |
| source_id | 49 |
| spelling | SZONDY, Zsuzsa REICHERT, Uwe BERNARDON, Jean-Michel MICHEL, Serge TÓTH, Réka KARÁSZI, Éva FÉSÜS, László 0264-6021 1470-8728 Portland Press Ltd. Cell Biology Molecular Biology Biochemistry http://dx.doi.org/10.1042/bj3310767 <jats:p>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 RARα, because (1) it can be reproduced by various RARα analogues both in vitro and in vivo, (2) the effect of RAs can be inhibited by the addition of an RARα antagonist, (3) CD4+CD8+thymocytes, which die on TCR stimulation, express RARα. Stimulation of RARγ, in contrast, enhances the activation-induced death of thymocytes and inhibits its prevention by RARα stimulation. RXR co-stimulation suspends this inhibitory effect of RARγ and permits the preventive function of RARα 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 RARα-mediated inhibitory and the RARγ-mediated enhancing pathways are in balance, whereas if 9-cis-RA is formed, additional stimulation of RXRs permits the inhibitory action of RARα.</jats:p> Inhibition of activation-induced apoptosis of thymocytes by all-trans- and 9-cis-retinoic acid is mediated via retinoic acid receptor α Biochemical Journal |
| spellingShingle | SZONDY, Zsuzsa, REICHERT, Uwe, BERNARDON, Jean-Michel, MICHEL, Serge, TÓTH, Réka, KARÁSZI, Éva, FÉSÜS, László, Biochemical Journal, Inhibition of activation-induced apoptosis of thymocytes by all-trans- and 9-cis-retinoic acid is mediated via retinoic acid receptor α, Cell Biology, Molecular Biology, Biochemistry |
| title | Inhibition of activation-induced apoptosis of thymocytes by all-trans- and 9-cis-retinoic acid is mediated via retinoic acid receptor α |
| title_full | Inhibition of activation-induced apoptosis of thymocytes by all-trans- and 9-cis-retinoic acid is mediated via retinoic acid receptor α |
| title_fullStr | Inhibition of activation-induced apoptosis of thymocytes by all-trans- and 9-cis-retinoic acid is mediated via retinoic acid receptor α |
| title_full_unstemmed | Inhibition of activation-induced apoptosis of thymocytes by all-trans- and 9-cis-retinoic acid is mediated via retinoic acid receptor α |
| title_short | Inhibition of activation-induced apoptosis of thymocytes by all-trans- and 9-cis-retinoic acid is mediated via retinoic acid receptor α |
| title_sort | inhibition of activation-induced apoptosis of thymocytes by all-trans- and 9-cis-retinoic acid is mediated via retinoic acid receptor α |
| title_unstemmed | Inhibition of activation-induced apoptosis of thymocytes by all-trans- and 9-cis-retinoic acid is mediated via retinoic acid receptor α |
| topic | Cell Biology, Molecular Biology, Biochemistry |
| url | http://dx.doi.org/10.1042/bj3310767 |