PMID: 9187263Jun 1, 1997Paper

Induction of apoptosis by retinoids and retinoic acid receptor gamma-selective compounds in mouse thymocytes through a novel apoptosis pathway

Molecular Pharmacology
Zsuzsa SzondyL Fésüs

Abstract

Retinoic acids are morphogenic signaling molecules that are derived from vitamin A and involved in a variety of tissue functions. Two groups of their nuclear receptors have been identified: retinoic acid receptors (RARs) and retinoic acid X receptors (RXRs). All-trans retinoic acid is the high affinity ligand for RARs, and 9-cis retinoic acid also binds to RXRs with high affinity. In cells at high concentrations, all-trans retinoic acid can be converted to 9-cis retinoic acid via unknown mechanisms. It was previously shown that retinoic acids prevents activation-induced death of thymocytes. Here, we report that both all-trans and 9-cis retinoic acid induce apoptosis of mouse thymocytes and purified CD4+CD8+ cells in ex vivo cultures, with 9-cis retinoic acid being 50 times more effective. The induction of apoptosis by retinoic acids is mediated by RARgamma because (a) the phenomenon can be reproduced only by RARgamma-selective retinoic acid analogs, (b) the cell death induced by either retinoic acids or RARgamma analogs can be inhibited by RARgamma-specific antagonists, and (c) CD4+CD8+ thymocytes express RARgamma. In vivo administration of an RARgamma analog resulted in thymus involution with the concomitant activation of the ...Continue Reading

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Citations

Dec 19, 2007·European Journal of Immunology·Ildikó KissZsuzsa Szondy
May 12, 2016·Annual Review of Immunology·Alexandre Larange, Hilde Cheroutre
Sep 11, 2019·The Journal of Nutrition·Shaikh M AhmadCharles B Stephensen
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May 16, 2012·European Journal of Immunology·Zsuzsa SzondyKrisztina Köröskényi
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Jan 23, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mohamed R AbdelaalHesham Haffez

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis