Limits...
The effect of alcohol and hydrogen peroxide on liver hepcidin gene expression in mice lacking antioxidant enzymes, glutathione peroxidase-1 or catalase.

Harrison-Findik DD, Lu S - Biomolecules (2015)

Bottom Line: Gpx-1(-/-) displayed significantly higher hepatic H2O2 levels than catalase(-/-) compared to wild-type mice, as measured by 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA).In conclusion, our findings strongly suggest that H2O2 inhibits hepcidin expression in vivo.Synergistic induction of CHOP by alcohol and H2O2, in the absence of gpx-1, stimulates liver hepcidin gene expression by ER stress independent of CREBH.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Division of Gastroenterology/Hepatology, University of Nebraska Medical Center, Omaha, NE 68198, USA. dharrisonfindik@unmc.edu.

ABSTRACT
This study investigates the regulation of hepcidin, the key iron-regulatory molecule, by alcohol and hydrogen peroxide (H2O2) in glutathione peroxidase-1 (gpx-1(-/-)) and catalase (catalase(-/-)) knockout mice. For alcohol studies, 10% ethanol was administered in the drinking water for 7 days. Gpx-1(-/-) displayed significantly higher hepatic H2O2 levels than catalase(-/-) compared to wild-type mice, as measured by 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). The basal level of liver hepcidin expression was attenuated in gpx-1(-/-) mice. Alcohol increased H2O2 production in catalase(-/-) and wild-type, but not gpx-1(-/-), mice. Hepcidin expression was inhibited in alcohol-fed catalase(-/-) and wild-type mice. In contrast, alcohol elevated hepcidin expression in gpx-1(-/-) mice. Gpx-1(-/-) mice also displayed higher level of basal liver CHOP protein expression than catalase(-/-) mice. Alcohol induced CHOP and to a lesser extent GRP78/BiP expression, but not XBP1 splicing or binding of CREBH to hepcidin gene promoter, in gpx-1(-/-) mice. The up-regulation of hepatic ATF4 mRNA levels, which was observed in gpx-1(-/-) mice, was attenuated by alcohol. In conclusion, our findings strongly suggest that H2O2 inhibits hepcidin expression in vivo. Synergistic induction of CHOP by alcohol and H2O2, in the absence of gpx-1, stimulates liver hepcidin gene expression by ER stress independent of CREBH.

Show MeSH

Related in: MedlinePlus

H2O2 and/or alcohol-mediated regulation of hepatic hepcidin gene expression. The signs, − and + indicate inhibition and induction of gene expression, respectively, and X represents the lack of CREBH or C/EBPα involvement in the induction of hepatic hepcidin gene expression.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4496697&req=5

biomolecules-05-00793-f008: H2O2 and/or alcohol-mediated regulation of hepatic hepcidin gene expression. The signs, − and + indicate inhibition and induction of gene expression, respectively, and X represents the lack of CREBH or C/EBPα involvement in the induction of hepatic hepcidin gene expression.


The effect of alcohol and hydrogen peroxide on liver hepcidin gene expression in mice lacking antioxidant enzymes, glutathione peroxidase-1 or catalase.

Harrison-Findik DD, Lu S - Biomolecules (2015)

H2O2 and/or alcohol-mediated regulation of hepatic hepcidin gene expression. The signs, − and + indicate inhibition and induction of gene expression, respectively, and X represents the lack of CREBH or C/EBPα involvement in the induction of hepatic hepcidin gene expression.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496697&req=5

biomolecules-05-00793-f008: H2O2 and/or alcohol-mediated regulation of hepatic hepcidin gene expression. The signs, − and + indicate inhibition and induction of gene expression, respectively, and X represents the lack of CREBH or C/EBPα involvement in the induction of hepatic hepcidin gene expression.
Bottom Line: Gpx-1(-/-) displayed significantly higher hepatic H2O2 levels than catalase(-/-) compared to wild-type mice, as measured by 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA).In conclusion, our findings strongly suggest that H2O2 inhibits hepcidin expression in vivo.Synergistic induction of CHOP by alcohol and H2O2, in the absence of gpx-1, stimulates liver hepcidin gene expression by ER stress independent of CREBH.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Division of Gastroenterology/Hepatology, University of Nebraska Medical Center, Omaha, NE 68198, USA. dharrisonfindik@unmc.edu.

ABSTRACT
This study investigates the regulation of hepcidin, the key iron-regulatory molecule, by alcohol and hydrogen peroxide (H2O2) in glutathione peroxidase-1 (gpx-1(-/-)) and catalase (catalase(-/-)) knockout mice. For alcohol studies, 10% ethanol was administered in the drinking water for 7 days. Gpx-1(-/-) displayed significantly higher hepatic H2O2 levels than catalase(-/-) compared to wild-type mice, as measured by 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). The basal level of liver hepcidin expression was attenuated in gpx-1(-/-) mice. Alcohol increased H2O2 production in catalase(-/-) and wild-type, but not gpx-1(-/-), mice. Hepcidin expression was inhibited in alcohol-fed catalase(-/-) and wild-type mice. In contrast, alcohol elevated hepcidin expression in gpx-1(-/-) mice. Gpx-1(-/-) mice also displayed higher level of basal liver CHOP protein expression than catalase(-/-) mice. Alcohol induced CHOP and to a lesser extent GRP78/BiP expression, but not XBP1 splicing or binding of CREBH to hepcidin gene promoter, in gpx-1(-/-) mice. The up-regulation of hepatic ATF4 mRNA levels, which was observed in gpx-1(-/-) mice, was attenuated by alcohol. In conclusion, our findings strongly suggest that H2O2 inhibits hepcidin expression in vivo. Synergistic induction of CHOP by alcohol and H2O2, in the absence of gpx-1, stimulates liver hepcidin gene expression by ER stress independent of CREBH.

Show MeSH
Related in: MedlinePlus