Bach1 deficiency ameliorates hepatic injury in a mouse model.
Bach1 is a basic region-leucine zipper (bZip) protein that forms heterodimers with the small Maf proteins and functions as a repressor of gene expression. One of the target genes of Bach1 is Hmox-1 that encodes heme oxygenase-1 (HO-1). HO-1 degrades heme into carbon monoxide (CO), biliverdin, and iron. HO-1 is strongly induced by various stresses as well as its substrate heme, and protects cells and tissues against insults through diverse cytoprotective functions of the reaction products CO and biliverdin. Bach1-deficiency in mice leads to higher expression of Hmox-1 in various tissues. Here we investigated the effects of Bach1-deficiency in mice on tissue injuries: hepatic injury induced by D-galactosamine (GalN) and lipopolysaccharide (LPS), and mouse paw edema induced by carrageenin, polysaccharide derived from various seaweeds. Bach1-deficiency suppressed induction of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in response to the GalN/LPS-treatment. However, production of tumor necrosis factor alpha (TNF-alpha) and nitric oxide (NO), both being cytotoxic mediators in LPS-induced hepatic injury, in Bach1-deficient mice and their peritoneal macrophages was similar to wild type controls. In contrast, Bach1-deficiency did not affect extent of mouse paw edema induced by carrageenin, which enhances vascular permeability by activating kinin release. These results indicate that Bach1 plays an inhibitory role in the cytoprotection of LPS-induced liver injury but not in the kinin-mediated inflammatory edema. The inhibitory role for Bach1 may stem from its activity to repress gene expression including HO-1.
Iida
Akio
A
Japan Tobacco Inc., Central Pharmaceutical Research Institute, Osaka, Japan.
Inagaki
Koji
K
Miyazaki
Akira
A
Yonemori
Fumihiko
F
Ito
Etsuro
E
Igarashi
Kazuhiko
K
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D050976:Basic-Leucine Zipper Transcription Factors / Q000172:deficiency*; D002351:Carrageenan; D004487:Edema / Q000473:pathology*; D005688:Galactosamine; D005786:Gene Expression Regulation / Q000235:genetics*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C486316:Bach1 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D005688:Galactosamine; D002351:Carrageenan; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase