Alteration of SREBP activation in liver of trisomy 21 fetuses.
We previously reported that trisomy 21 (T21) fetuses have an intrinsic lipid metabolism abnormality resulting in higher serum cholesterol levels than their matched controls. In an attempt to clarify the biochemical basis of this derangement we analyzed the liver cholesterol levels and activation of the sterol regulatory element binding proteins SREBP-1 and SREBP-2. We report here for the first time that SREBP-1 and SREBP-2 are present in human fetal liver and their activation follows a different regulatory pattern. Moreover T21 fetuses show a peculiar pattern of SREBP activation which, at variance from control fetuses, involves sterol-independent maturation of SREBP-1. Multiple defects accompanied the lipid derangement in T21, resulting in high circulating and tissue cholesterol. This may serve as an early biochemical marker of an unknown, possibly genetically determined mechanism, whose consequence on lipid homeostasis during postnatal and adult life is still not understood.
Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche "Mario Negri,", Milan, 20157, Italy. diomede@irfmn.mn.mnegri.it
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Diomede
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Salmona
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Albani
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Bianchi
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Bruno
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Salmona
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Nicolini
D015153:Blotting, Western; D022762:CCAAT-Enhancer-Binding Proteins; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004314:Down Syndrome; D006706:Homeostasis; D006801:Humans; D008099:Liver / Q000196:embryology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors / Q000378:metabolism*
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C497387:SREBF1 protein, human; C497390:SREBF2 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors; D002784:Cholesterol