Reactive oxygen species derived from NADPH oxidase system is not essential for liver regeneration after partial hepatectomy.
BACKGROUND
There is suggestive evidence that reactive oxygen species may play a role in the initiation of liver regeneration via a kupffer cell-mediated mechanism involving TNFa and NF-kappa B. In mammalian cells, a major source of reactive oxygen species derives from the membrane-bound NADPH oxidase system (no protein de novo synthesis is required) and it is known that the low levels of oxidants produced through NADPH oxidase play a role in liver cell proliferation because of peroxisome proliferators.


METHODS
We used knockout mice lacking Cybb: subunit of NADPH oxidase to determine whether signaling at the start of liver regeneration after partial hepatectomy (PH) involves reactive oxygen species produced through NADPH oxidase and to analyze in more detail the abnormalities caused by lack of its component, which is required for the initiation of liver regeneration.


RESULTS
Lack of Cybb had little effect on NF-kappa B and STAT3 binding, and no effect in TNFa and interleukin-6 production after PH. Cybb KO mice had normal liver structure and similar levels of hepatocyte DNA replication as those of wild type mice.


CONCLUSIONS
We conclude that NADPH oxidase is not necessary for liver regeneration after PH. It is likely that there is a potential pathway not including NADPH oxidase to activate NF-kappa B and STAT3 binding for the initiation of liver regeneration after PH.
Ueno
Shinichi
S
Department of Pathology, University of Washington School of Medicine, Seattle, Washington, USA. ueno1@kufm.kagoshima-u.ac.jp
Campbell
Jean
J
Fausto
Nelson
N
D000818:Animals; D004261:DNA Replication / Q000502:physiology; D006498:Hepatectomy / Q000379:methods*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology / Q000201:enzymology* / Q000601:surgery; D008115:Liver Regeneration / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D015850:Interleukin-6; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases