Deficiency of manganese superoxide dismutase in hepatocytes disrupts zonated gene expression in mouse liver

Jacek Lenart, Frank Dombrowski, Agnes Görlach, Thomas Kietzmann

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

21 Zitate (Scopus)

Abstract

The liver acinus displays a physiological periportal to perivenous oxygen gradient. This gradient was implicated to use reactive oxygen species (ROS) as mediators for the zonal gene expression. Mitochondria use oxygen and produce ROS, therefore they may contribute to the zonation of gene expression. To further elucidate this, we used the Cre-loxP system to generate a hepatocyte-specific null mutation of the mitochondrial antioxidant enzyme manganese superoxide dismutase (MnSOD) in mice. We found that ROS levels were enhanced in livers of MnSOD-/- mice which were reduced in size and displayed signs of liver failure such as intracellular protein droplets, increased apoptotic bodies and Bax levels as well as multinuclear hepatocytes. Further, the zonation of glutamine synthetase, glucokinase and phosphoenolpyruvate carboxykinase was no longer preserved. We conclude that deficiency of mitochondrial MnSOD initiates a dysregulation of zonated gene expression in liver.

OriginalspracheEnglisch
Seiten (von - bis)238-244
Seitenumfang7
FachzeitschriftArchives of Biochemistry and Biophysics
Jahrgang462
Ausgabenummer2
DOIs
PublikationsstatusVeröffentlicht - 15 Juni 2007

Fingerprint

Untersuchen Sie die Forschungsthemen von „Deficiency of manganese superoxide dismutase in hepatocytes disrupts zonated gene expression in mouse liver“. Zusammen bilden sie einen einzigartigen Fingerprint.

Dieses zitieren