p66Shc has a pivotal function in impaired liver regeneration in aged mice by a redox-dependent mechanism

Haga, Sanae; Morita, Naoki; Irani, Kaikobad; Fujiyoshi, Masato; Ogino, Tetsuya; Ozawa, Takeaki; Ozaki, Michitaka

p66Shc has a pivotal function in impaired liver regeneration in aged mice by a redox-dependent mechanism

Haga, Sanae; Morita, Naoki; Irani, Kaikobad et al.

Laboratory Investigation, 2010, 90(12), 1718-1726

Permalink : https://hdl.handle.net/2115/45537

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アクセス権	open access
URI	https://hdl.handle.net/2115/45537
タイトル	p66Shc has a pivotal function in impaired liver regeneration in aged mice by a redox-dependent mechanism
著者	Haga, Sanae ; Morita, Naoki ; Irani, Kaikobad ; Fujiyoshi, Masato ; Ogino, Tetsuya ; Ozawa, Takeaki ; Ozaki, Michitaka
著者名 Haga, Sanae
著者名 Morita, Naoki
著者名 Irani, Kaikobad
著者名 Fujiyoshi, Masato
著者名 Ogino, Tetsuya
著者名 Ozawa, Takeaki
著者名 Ozaki, Michitaka
言語	英語
キーワード	Akt
	apoptosis
	caspase-3
	in vivo imaging
	oxidative stress
	p66Shc
発行日	2010-12
出版者	Nature Publishing Group
収録物名	Laboratory Investigation
巻(号)	90(12)
ページ	1718-1726
抄録	Liver regeneration involves complicated processes and is affected by various patho-physiological conditions. The present 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 (MAPK, STAT-3, p46/52Shc) and anti-oxidation (catalase, SOD, Ref-1, GPx) 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. p66Shc, known as an age-/oxidant-associated protein, was strongly phosphorylated. By knocking-down p66Shc, the impairment of liver regeneration was normalized. OS immediately after hepatectomy induced subsequent liver injury (apoptosis), and deletion of p66Shc 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, p66Shc may play a pivotal role in the impairment of liver regeneration in aged mice by triggering OS and subsequent apoptosis. The present data may provide a clue to understanding the mechanism underlying the association between aging and the impairment of liver regeneration.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
PISSN	0023-6837
関連情報	PMID 20567235
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1038/labinvest.2010.119