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Status: Bibliographieeintrag

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Verfasst von:Matsuo, Shunsuke [VerfasserIn]   i
 Ogawa, Masayuki [VerfasserIn]   i
 Muckenthaler, Martina [VerfasserIn]   i
 Mizui, Yumiko [VerfasserIn]   i
 Sasaki, Shota [VerfasserIn]   i
 Fujimura, Takafumi [VerfasserIn]   i
 Takizawa, Masayuki [VerfasserIn]   i
 Ariga, Nagayuki [VerfasserIn]   i
 Ozaki, Hiroaki [VerfasserIn]   i
 Sakaguchi, Masakiyo [VerfasserIn]   i
 Gonzalez, Frank J. [VerfasserIn]   i
 Inoue, Yusuke [VerfasserIn]   i
Titel:Hepatocyte nuclear factor 4α controls iron metabolism and regulates transferrin receptor 2 in mouse liver
Verf.angabe:Shunsuke Matsuo, Masayuki Ogawa, Martina U. Muckenthaler, Yumiko Mizui, Shota Sasaki, Takafumi Fujimura, Masayuki Takizawa, Nagayuki Ariga, Hiroaki Ozaki, Masakiyo Sakaguchi, Frank J. Gonzalez, and Yusuke Inoue
E-Jahr:2015
Jahr:November 2, 2015
Umfang:12 S.
Fussnoten:Gesehen am 09.06.2020
Titel Quelle:Enthalten in: JBC papers in press
Ort Quelle:Bethesda, MD. : American Soc. for Biochemistry and Molecular Biology, 2003
Jahr Quelle:2015
Band/Heft Quelle:290(2015), 52, Seite 30855-30865
ISSN Quelle:1083-351X
Abstract:Iron is an essential element in biological systems, but excess iron promotes the formation of reactive oxygen species, resulting in cellular toxicity. Several iron-related genes are highly expressed in the liver, a tissue in which hepatocyte nuclear factor 4α (HNF4α) plays a critical role in controlling gene expression. Therefore, the role of hepatic HNF4α in iron homeostasis was examined using liver-specific HNF4α-null mice (Hnf4aΔH mice). Hnf4aΔH mice exhibit hypoferremia and a significant change in hepatic gene expression. Notably, the expression of transferrin receptor 2 (Tfr2) mRNA was markedly decreased in Hnf4aΔH mice. Promoter analysis of the Tfr2 gene showed that the basal promoter was located at a GC-rich region upstream of the transcription start site, a region that can be transactivated in an HNF4α-independent manner. HNF4α-dependent expression of Tfr2 was mediated by a proximal promoter containing two HNF4α-binding sites located between the transcription start site and the translation start site. Both the GC-rich region of the basal promoter and the HNF4α-binding sites were required for maximal transactivation. Moreover, siRNA knockdown of HNF4α suppressed TFR2 expression in human HCC cells. These results suggest that Tfr2 is a novel target gene for HNF4α, and hepatic HNF4α plays a critical role in iron homeostasis.
DOI:doi:10.1074/jbc.M115.694414
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: https://doi.org/10.1074/jbc.M115.694414
 Volltext: http://www.jbc.org/content/290/52/30855
 DOI: https://doi.org/10.1074/jbc.M115.694414
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:hepcidin
 HNF4α
 hypoferremia
 iron metabolism
 liver
 nuclear receptor
 transcription regulation
 transferrin
 transferrin receptor 2
K10plus-PPN:1700202871
Verknüpfungen:→ Zeitschrift

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