Transcriptional activation of CYP2C, MxA and Fas in sudden infant death syndrome.
The expression of cytochrome P4502C has been shown to be upregulated in sudden infant death syndrome (SIDS) and could be linked to viral infection through the release of interferon alpha and interleukins. MxA is a reliable marker of IFNalpha release and its level was significantly enhanced in SIDS reflecting the release of IFNalpha in response to viral infection. Similarly, the concentration of Fas protein was increased in SIDS (2.6x control) and indicated a stimulation of the Fas gene expression. Accumulation of MxA and Fas proteins were visible in liver and to a lesser extent in lung and kidney. The amount of RNA encoding CYP2C9 (4.4x control), 2C8 (2.5x) and 2C18 (2.3x) was markedly higher in SIDS than in age-matched children and would suggest a transcriptional activation of CYP2C gene expression. Finally, CYP2C genes were shown to be adjacent to two IFN-inducible genes (IFI54 and IFI56) on chromosome 10. We conclude that in SIDS a viral infection leads to the release of IFNalpha which could activate a battery of IFN-inducible genes. This might modify the chromatin structure and facilitate the accessibility to promoter/regulatory sequences of CYP2C and Fas genes close to IFN-inducible gene on chromosome 10.
Beurton
F
F
INSERM U75, Université René Descartes, 75730 Paris Cedex 15, France.
Gueret
G
G
Horisberger
M
M
Cheron
G
G
Cresteil
T
T
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D051017:Apoptosis Regulatory Proteins; D001189:Aryl Hydrocarbon Hydroxylases; D002352:Carrier Proteins; D002874:Chromosome Mapping; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D019204:GTP-Binding Proteins; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007231:Infant, Newborn; D016898:Interferon-alpha / Q000378:metabolism; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008168:Lung / Q000196:embryology / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000235:genetics*; D064547:Myxovirus Resistance Proteins; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000235:genetics; D013398:Sudden Infant Death / Q000235:genetics*; D014018:Tissue Distribution; D015533:Transcriptional Activation; D019014:fas Receptor / Q000235:genetics* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C484290:IFIT1 protein, human; C484289:IFIT2 protein, human; D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D019014:fas Receptor; D012313:RNA; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D013250:Steroid Hydroxylases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C082185:CYP2C18 protein, human; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D039181:Steroid 16-alpha-Hydroxylase; D019204:GTP-Binding Proteins