Cytochrome P-450 expression in sudden infant death syndrome.
In the human liver, the major rise of the cytochrome P-450 isoform content occurs during the first months following birth (e.g., the high vulnerability period to sudden infant death syndrome (SIDS), a syndrome frequently associated with viral infection and drug hypersensitivity. We examined the expression of individual P-450 isoforms in liver samples collected postmortem from SIDS infants and compared values with those of control adults and children of the same age suffering from various pathologies. Hepatic microsomes were prepared and examined for their content in total P-450, the level of individual isoforms (CYP1A2, CYP2E1, CYP4A, CYP3A, and CYP2C) determined with specific antibodies and for their enzymatic activities. Total RNA was extracted and probed with several CYP cDNAs and oligomers. The overall hepatic P-450 content was not modified in SIDS infants. Among cytochrome P-450 isoforms, only CYP2C was markedly increased. This rise resulted from an accumulation of RNA encoding CYP2C and was associated with a stimulation of diazepam demethylation. The precocious expression of CYP2C in SIDS could result in a higher production of epoxyeicosatrienoic acids in the neonate, believed to act as relaxant of pulmonary smooth muscles. Its consequence might be the induction of fatal apnea in SIDS.
Treluyer
J M
JM
INSERM U75, Université René Descartes, Paris, France.
Cheron
G
G
Sonnier
M
M
Cresteil
T
T
D001483:Base Sequence; D015153:Blotting, Western; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D003645:Death, Sudden; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008099:Liver / Q000737:chemistry*; D008969:Molecular Sequence Data
D003577:Cytochrome P-450 Enzyme System