Transcriptional activation of heme oxygenase-1 gene in mouse spleen, liver and kidney cells after treatment with lipopolysaccharide or hemoglobin.
Heme oxygenase (HO)-1 catalyzes the conversion of heme to biliverdin, iron and carbon monoxide. HO-1 is induced by many reagents including heme, Hb and lipopolysaccharide (LPS). LPS is known to activate the HO-1 gene in cultured mouse liver and macrophage cells through oxidative activation of NF-kappaB. But little is known about the effect of LPS and Hb on the HO-1 gene in living organisms. To study this issue, we examined the HO-1 and its mRNA levels in mouse liver, spleen and kidney after intravenous administration of LPS and Hb. On LPS treatment, the amount of HO-1 and its mRNA increased markedly mainly in mouse spleen, but on Hb treatment the amounts of HO-1 and its mRNA increased slightly only in liver. Run-off transcription assay supported the above results and band shift assays also revealed that LPS significantly activates an NF-kappaB-like factor in spleen cells, while Hb slightly activates it in liver cells. According to our previous study, a small amount of Hb injected to mouse is selectively taken up by liver as Hb-haptoglobin complex. These results suggest different pathways for the HO gene activation in mouse organs; one by LPS in spleen cells and the other by Hb in liver cells.
Oshiro
S
S
Department of Biochemical Genetics, Medical Research Institute, Tokyo Medical and Dental University, Japan.
Takeuchi
H
H
Matsumoto
M
M
Kurata
S
S
D000818:Animals; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis* / Q000235:genetics; D051547:Heme Oxygenase-1; D006454:Hemoglobins / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology*; D008565:Membrane Proteins; D051379:Mice; D009928:Organ Specificity; D013154:Spleen / Q000201:enzymology*; D015533:Transcriptional Activation / Q000187:drug effects
D006454:Hemoglobins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse