PMID- 19812349
OWN - NLM
STAT- MEDLINE
DCOM- 20100319
LR  - 20231213
IS  - 1521-009X (Electronic)
IS  - 0090-9556 (Print)
IS  - 0090-9556 (Linking)
VI  - 38
IP  - 1
DP  - 2010 Jan
TI  - Gene regulation of CYP4F11 in human keratinocyte HaCaT cells.
PG  - 100-7
LID - 10.1124/dmd.109.029025 [doi]
AB  - Mechanisms regulating CYP4F genes remain under investigation, although 
      characterization of CYP4F regulatory modalities would facilitate the discovery of 
      new drug targets. This present study shows that all-trans- and 9-cis-retinoic 
      acids can inhibit CYP4F11 expression in human keratinocyte-derived HaCaT cells. 
      Transrepression of many genes by retinoic acids is mediated by interactions 
      between retinoid receptors and the activator protein 1 (AP-1) complex. 
      Proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 
      1beta, which can activate the AP-1 complex, induce CYP4F11 transcription in HaCaT 
      cells. The c-Jun N-terminal kinase (JNK)-specific inhibitor 1,9-pyrazoloanthrone 
      (SP600125) blocked the induction of CYP4F11 by both cytokines, indicating 
      involvement of the JNK pathway. Furthermore, TNF-alpha failed to induce CYP4F11 
      transcription when HaCaT cells were preincubated with retinoic acids. Retinoic 
      acids are ligands for the retinoic acid receptors (RARs) and the retinoid X 
      receptors (RXRs). The RXR agonist 
      6-(1(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl) 
      nicotinic acid (LG268) greatly induced CYP4F11 transcription, whereas the RAR 
      agonist 
      4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic 
      acid (TTNPB) markedly inhibited CYP4F11 transcription, indicating that 
      down-regulation of CYP4F11 transcription by retinoic acid is mediated by RARs and 
      may also be related to ligand competition for RXRs. Thus, the CYP4F11 gene is 
      positively regulated by multiple signaling pathways in HaCaT keratinocytes, 
      including RXR and JNK signaling pathways.
FAU - Wang, Ying
AU  - Wang Y
AD  - Department of Biochemistry and Molecular Biology, the University of Texas-Houston 
      Medical School, Houston, Texas, USA.
FAU - Bell, Jordan C
AU  - Bell JC
FAU - Keeney, Diane S
AU  - Keeney DS
FAU - Strobel, Henry W
AU  - Strobel HW
LA  - eng
GR  - R01 AR045603/AR/NIAMS NIH HHS/United States
GR  - R01 NS044174/NS/NINDS NIH HHS/United States
GR  - AR45603/AR/NIAMS NIH HHS/United States
GR  - NS44174/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Drug Metab Dispos
JT  - Drug metabolism and disposition: the biological fate of chemicals
JID - 9421550
RN  - 0 (Anthracenes)
RN  - 0 (Benzoates)
RN  - 0 (Interleukin-1alpha)
RN  - 0 (Nicotinic Acids)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (RARA protein, human)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoic Acid Receptor alpha)
RN  - 0 (Retinoid X Receptor alpha)
RN  - 0 (Retinoid X Receptor beta)
RN  - 0 (Retinoids)
RN  - 0 (Tetrahydronaphthalenes)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1TW30Y2766 (pyrazolanthrone)
RN  - 1UA8E65KDZ (Alitretinoin)
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  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 1.14.14.1 (Cytochrome P450 Family 4)
RN  - EC 1.14.14.78 (CYP4F11 protein, human)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - UVU4X1103P (LG 100268)
SB  - IM
MH  - Alitretinoin
MH  - Anthracenes/pharmacology
MH  - Benzoates/pharmacology
MH  - Cell Line
MH  - Cytochrome P-450 Enzyme System/*genetics/metabolism
MH  - Cytochrome P450 Family 4
MH  - Gene Expression/drug effects/genetics
MH  - Gene Expression Regulation/drug effects/*genetics
MH  - Humans
MH  - Interleukin-1alpha/pharmacology
MH  - JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
MH  - Keratinocytes/drug effects/*metabolism
MH  - Nicotinic Acids/pharmacology
MH  - Phosphorylation/drug effects
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Receptors, Retinoic Acid/agonists/genetics/metabolism
MH  - Retinoic Acid Receptor alpha
MH  - Retinoid X Receptor alpha/agonists/genetics/metabolism
MH  - Retinoid X Receptor beta/agonists/genetics/metabolism
MH  - Retinoids/pharmacology
MH  - Signal Transduction/drug effects/genetics
MH  - Tetrahydronaphthalenes/pharmacology
MH  - Tretinoin/pharmacology
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Retinoic Acid Receptor gamma
PMC - PMC2802424
EDAT- 2009/10/09 06:00
MHDA- 2010/03/20 06:00
PMCR- 2011/01/01
CRDT- 2009/10/09 06:00
PHST- 2009/10/09 06:00 [entrez]
PHST- 2009/10/09 06:00 [pubmed]
PHST- 2010/03/20 06:00 [medline]
PHST- 2011/01/01 00:00 [pmc-release]
AID - dmd.109.029025 [pii]
AID - 029025 [pii]
AID - 10.1124/dmd.109.029025 [doi]
PST - ppublish
SO  - Drug Metab Dispos. 2010 Jan;38(1):100-7. doi: 10.1124/dmd.109.029025.