PMID- 7565709
OWN - NLM
STAT- MEDLINE
DCOM- 19951025
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 15
IP  - 10
DP  - 1995 Oct
TI  - 9-cis retinoic acid inhibition of activation-induced apoptosis is mediated via 
      regulation of fas ligand and requires retinoic acid receptor and retinoid X 
      receptor activation.
PG  - 5576-85
AB  - T-cell hybridomas, thymocytes, and T cells can be induced to undergo apoptotic 
      cell death by activation through the T-cell receptor. This process requires 
      macromolecular synthesis and thus gene expression, and it has been shown to be 
      influenced by factors regulating transcription. Recently, activation, T-cell 
      hybridomas rapidly express the Fas/CD95 receptor and its ligand, Fas ligand 
      (FasL), which interact to transduce the death signal in the activated cell. 
      Retinoids, the active metabolites of vitamin A, modulate expression of specific 
      target genes by binding to two classes of intracellular receptors, retinoic acid 
      receptors (RARs) and retinoid X receptors (RXRs). They are potent modulators of 
      apoptosis in a number of experimental models, and they have been shown to inhibit 
      activation-induced apoptosis in T-cell hybridomas and thymocytes. Particularly 
      effective is the prototypic pan-agonist 9-cis retinoic acid (9-cis RA), which has 
      high affinity for both RARs and RXRs. We report here that 9-cis RA inhibits 
      T-cell receptor-mediated apoptosis in T-cell hybridomas by blocking the 
      expression of Fas ligand following activation. This inhibition appears to be at 
      the level of FasL mRNA, with the subsequent failure to express cell surface FasL. 
      RAR-selective (TTNPB) or RXR-selective (LG100268) ligands alone were considerably 
      less potent than RAR-RXR pan-agonists. However, the addition of both RAR- and 
      RXR-selective ligands was as effective as the addition of 9-cis RA alone. The 
      demonstrates that the inhibitory effect requires the ligand-mediated activation 
      of both retinoid receptor signaling pathways.
FAU - Bissonnette, R P
AU  - Bissonnette RP
AD  - Department of Cell Biology, Ligand Pharmaceuticals, San Diego, California 92121, 
      USA.
FAU - Brunner, T
AU  - Brunner T
FAU - Lazarchik, S B
AU  - Lazarchik SB
FAU - Yoo, N J
AU  - Yoo NJ
FAU - Boehm, M F
AU  - Boehm MF
FAU - Green, D R
AU  - Green DR
FAU - Heyman, R A
AU  - Heyman RA
LA  - eng
GR  - GM52735/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Benzoates)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Fasl protein, mouse)
RN  - 0 (Interleukin-2)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Nicotinic Acids)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinoids)
RN  - 0 (Tetrahydronaphthalenes)
RN  - 0 (Transcription Factors)
RN  - 0 (fas Receptor)
RN  - 5688UTC01R (Tretinoin)
RN  - 71441-28-6 
      (4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic 
      acid)
RN  - UVU4X1103P (LG 100268)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/*physiology
MH  - Base Sequence
MH  - Benzoates/pharmacology
MH  - DNA Damage
MH  - Fas Ligand Protein
MH  - Hybridomas
MH  - Interleukin-2/biosynthesis
MH  - Membrane Glycoproteins/*biosynthesis/genetics
MH  - Mice
MH  - Molecular Sequence Data
MH  - Nicotinic Acids/pharmacology
MH  - RNA, Messenger/biosynthesis
MH  - Receptors, Retinoic Acid/*physiology
MH  - Retinoid X Receptors
MH  - Retinoids/pharmacology
MH  - Signal Transduction/physiology
MH  - T-Lymphocytes
MH  - Tetrahydronaphthalenes/pharmacology
MH  - Transcription Factors/*physiology
MH  - Transcriptional Activation
MH  - Tretinoin/*pharmacology
MH  - fas Receptor/genetics
PMC - PMC230808
EDAT- 1995/10/01 00:00
MHDA- 1995/10/01 00:01
PMCR- 1995/10/01
CRDT- 1995/10/01 00:00
PHST- 1995/10/01 00:00 [pubmed]
PHST- 1995/10/01 00:01 [medline]
PHST- 1995/10/01 00:00 [entrez]
PHST- 1995/10/01 00:00 [pmc-release]
AID - 10.1128/MCB.15.10.5576 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1995 Oct;15(10):5576-85. doi: 10.1128/MCB.15.10.5576.