Suppression of autophagy during liver regeneration impairs energy charge and hepatocyte senescence in mice

Takeo Toshima, Ken Shirabe, Takasuke Fukuhara, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Tetsuo Ikeda, Shinji Okano, Yoshihiko Maehara

研究成果: Contribution to journalArticle査読

55 被引用数 (Scopus)

抄録

Autophagy is a homeostatic mechanism that regulates protein and organelle turnover and uses the amino acids from degraded proteins to produce adenosine 5'-triphosphate (ATP). We investigated the activity of autophagy-associated pathways in liver regeneration after partial hepatectomy (PHx) in liver-specific autophagy-related gene 5 (Atg5) knockout (KO) mice. Liver regeneration was severely impaired by 70% PHx, with a reduction in postoperative mitosis, but a compensating increase in hepatocyte size. PHx induced intracellular adenosine triphosphate and β-oxidation reduction as well as injured cellular mitochondria. Furthermore, PHx in Atg5 KO mice enhanced hepatic accumulation of p62 and ubiquitinated proteins. These results indicated that reorganization of intracellular proteins and organelles during autophagy was impaired in the regenerating liver of these mice. Up-regulation of p21 was associated with hepatocyte senescence, senescence-associated β-galactosidase expression, irreversible growth arrest, and secretion of senescence-associated molecules, including interleukin (IL)-6 and IL-8. Conclusion: These findings indicate that autophagy plays a critical role in liver regeneration and in the preservation of cellular quality, preventing hepatocytes from becoming fully senescent and hypertrophic.

本文言語英語
ページ(範囲)290-300
ページ数11
ジャーナルHepatology
60
1
DOI
出版ステータス出版済み - 7 2014

All Science Journal Classification (ASJC) codes

  • Hepatology

フィンガープリント 「Suppression of autophagy during liver regeneration impairs energy charge and hepatocyte senescence in mice」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

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