TAILIEUCHUNG - Báo cáo y học: Identification of an element within the promoter of human selenoprotein P responsive to transforming growth factor-b

Selenoprotein P (SeP) is a plasma protein that contains up to 10 selenocysteine residues and accounts for about 50% of total selenium in human plasma. We have previously shown that SeP expression in the human liver cell line HepG2 is inhibited by transforming growth factor (TGF)-b1 on a transcriptional level. Smad proteins are the transcriptional mediators of TGF-b signalling and putative Smad-binding elements (SBE) comprising the core sequence CAGACA are present at two positions in the SeP promoter | Eur. J. Biochem. 268 6176-6181 2001 FEBS 2001 Identification of an element within the promoter of human selenoprotein P responsive to transforming growth factor-b Volker Mostert1 Sandra Wolff1 Inaebora Dreher2 Josef Kohrle2 and Josef Abel1 1Medizinisches Institutfur Umwelthygiene an der Heinrich-Heine-Universitat Dusseldorf Abteilung Experimentelle Toxikologie Dusseldorf Germany 2Medizinische Poliklinik Universitat Wurzburg Wurzburg Germany Selenoprotein P SeP is a plasma protein that contains up to 10 selenocysteine residues and accounts for about 50 of total selenium in human plasma. We have previously shown that SeP expression in the human liver cell line HepG2 is inhibited by transforming growth factor TGF -b1 on a transcriptional level. Smad proteins are the transcriptional mediators of TGF-b signalling and putative Smad-binding elements SBE comprising the core sequence CAGACA are present at two positions in the SeP promoter. The aim of our study was to investigate whether Smad molecules are involved in inhibition of SeP expression by TGF-p1 and to locate the promoter region critical for this effect. As seen in electrophoretic-mobility-shift assays TGF-p1 treatment led to enhanced binding of nuclear proteins to a putative SBE from the SeP promoter. Overexpression of Smad 3 and 4 but not of Smad 2 resulted in a marked down-regulation of SeP mRNA expression. Similar effects were observed for luciferase expression under control of a human SeP-promoter construct. Deletion as well as point-mutation of putative SBEs led to a loss of promoter sensitivity towards TGF-p1 treatment. Hence we demonstrated an involvement of Smad 3 and 4 in transcriptional regulation of SeP by TGF-p1 and we were able to identify the TGF-p-responsive element in the SeP promoter. Keywords selenoprotein P transforming growth factor-p1 Smad promoter CAGA box. Selenoprotein P SeP is a selenocysteine-containing glycoprotein that accounts for about 50 of total plasma selenium in humans reviewed .

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