Journal article
p66(Shc) has a pivotal function in impaired liver regeneration in aged mice by a redox-dependent mechanism
Laboratory investigation, Vol.90(12), pp.1718-1726
12/2010
DOI: 10.1038/labinvest.2010.119
PMID: 20567235
Abstract
Liver regeneration involves complicated processes and is affected by various patho-physiological conditions. This study was designed to examine the molecular mechanisms underlying the aging-associated impairment of liver regeneration. Male C57BL/6J mice were used as young and aged mice (<10 weeks and >20 months old, respectively). These mice were subjected to 70% partial hepatectomy (PH). Liver regeneration and liver injury/stresses were evaluated chronologically after PH. Post-hepatectomy liver regeneration was markedly impaired in aged mice. Though the extent of hepatocyte proliferation in the regenerating liver was similar in aged and young mice, cell growth was absent in aged mice. Oxidative stress (OS) was observed immediately after hepatectomy, followed by marked apoptosis in aged mice. Signaling molecules regarding cell proliferation (mitogen-activated protein kinase, STAT3, p46/52(Shc)) and anti-oxidation (catalase, superoxide dismutase, Ref-1, glutathione peroxidase) were expressed/activated after hepatectomy in livers of both aged and young mice. Akt was not activated in aged-mouse liver, but its expression was similar to that in young mice. p66(Shc), known as an age-/oxidant-associated protein, was strongly phosphorylated. By knocking down p66(Shc), the impairment of liver regeneration was normalized. OS immediately after hepatectomy induced subsequent liver injury (apoptosis), and deletion of p66(Shc) suppressed both OS and hepatocyte apoptosis in the regenerating liver of aged mice. Though we need additional data in other animal models to fully understand the mechanism, p66(Shc) may have a pivotal function in the impairment of liver regeneration in aged mice by triggering OS and subsequent apoptosis. This data may provide a clue to understanding the mechanism underlying the association between aging and the impairment of liver regeneration.
Details
- Title: Subtitle
- p66(Shc) has a pivotal function in impaired liver regeneration in aged mice by a redox-dependent mechanism
- Creators
- Sanae Haga - Department of Molecular Surgery, Hokkaido University School of Medicine, Sapporo, JapanNaoki MoritaKaikobad IraniMasato FujiyoshiTetsuya OginoTakeaki OzawaMichitaka Ozaki
- Resource Type
- Journal article
- Publication Details
- Laboratory investigation, Vol.90(12), pp.1718-1726
- DOI
- 10.1038/labinvest.2010.119
- PMID
- 20567235
- NLM abbreviation
- Lab Invest
- ISSN
- 0023-6837
- eISSN
- 1530-0307
- Publisher
- United States
- Language
- English
- Date published
- 12/2010
- Academic Unit
- Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984047872702771
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