Modulation of glucokinase expression by hypoxia-inducible factor 1 and upstream stimulatory factor 2 in primary rat hepatocytes
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| 024 | 7 | 0 | |a 10.1515/BC.2004.018 |2 doi |
| 035 | |a (NATIONALLICENCE)gruyter-10.1515/BC.2004.018 | ||
| 245 | 0 | 0 | |a Modulation of glucokinase expression by hypoxia-inducible factor 1 and upstream stimulatory factor 2 in primary rat hepatocytes |h [Elektronische Daten] |c [U. Roth, K. Jungermann, T. Kietzmann] |
| 520 | 3 | |a Glucokinase (GK) is the key enzyme of glucose utilization in liver and is localized in the less aerobic perivenous area. Until now, the O2-responsive elements in the liverspecific GK promoter are unknown, and therefore the aim of this study was to identify the O2-responsive element in this promoter. We found that the GK promoter sequence -87/-80 matched the binding site for hypoxia inducible factor 1 (HIF-1) and upstream stimulatory factor (USF). In primary rat hepatocytes we could show that venous pO2 enhanced HIF-1α and USF-2a levels, both of which activated GK expression. Furthermore, transfection experiments revealed that the GK sequence -87/-80 mediated the HIF-1α or USF-2-dependent activation of the GK promoter. The binding of HIF-1 and USF to the GKHRE was corroborated by electrophoretic mobility shift assay (EMSA). However, the maximal response to HIF-1α or USF was only achieved when constructs with the -87/ -80 sequence in context with a 39-36 bp native GK promoter sequence containing a hepatocyte nuclear factor 4 (HNF-4) binding site were used. HIF-1α and HNF-4 additively activated the GK promoter, while USF-2 and HNF-4 together did not show this additive activation. Thus, HIF-1 and USF may play differential roles in the modulation of GK expression in response to O2. | |
| 540 | |a Copyright © 2004 by Walter de Gruyter GmbH & Co. KG | ||
| 690 | 7 | |a Biochemistry |2 nationallicence | |
| 690 | 7 | |a Molecular biology |2 nationallicence | |
| 690 | 7 | |a Cellular biology |2 nationallicence | |
| 700 | 1 | |a Roth |D U. |4 aut | |
| 700 | 1 | |a Jungermann |D K. |4 aut | |
| 700 | 1 | |a Kietzmann |D T. |4 aut | |
| 773 | 0 | |t Biological Chemistry |d Walter de Gruyter |g 385/3-4(2004-04-13), 239-247 |x 1431-6730 |q 385:3-4<239 |1 2004 |2 385 |o bchm | |
| 856 | 4 | 0 | |u https://doi.org/10.1515/BC.2004.018 |q text/html |z Onlinezugriff via DOI |
| 908 | |D 1 |a research article |2 jats | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1515/BC.2004.018 |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Roth |D U. |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Jungermann |D K. |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Kietzmann |D T. |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Biological Chemistry |d Walter de Gruyter |g 385/3-4(2004-04-13), 239-247 |x 1431-6730 |q 385:3-4<239 |1 2004 |2 385 |o bchm | ||
| 900 | 7 | |b CC0 |u http://creativecommons.org/publicdomain/zero/1.0 |2 nationallicence | |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-gruyter | ||