Impaired activities of cyclic adenosine monophosphate-responsive element binding protein, protein kinase A and calcium-independent phospholipase A2 are involved in deteriorated regeneration of cirrhotic liver after partial hepatectomy in rats

Gang Zhao, Rie Wakabayashi, Shinya Shimoda, Yumi Fukunaga, Michiaki Kumagai, Masao Tanaka, kenji nakano

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Aims: This study is to elucidate whether cyclic adenosine monophosphate (cAMP)-mediated signal is involved in lower regenerative potential of cirrhotic liver. Methods: Hepatic cAMP concentration, activities of protein kinase A (PKA), c-AMP responsive element binding protein (CREB) and Ca2+-independent phospholipase A2 (iPLA2) and regeneration rate were compared between rats with thioacetamide-induced cirrhotic and normal livers after twothird hepatectomy. Results: The liver regeneration estimated by the rates of [3H]-thymidine incorporation and staining of proliferating cell nuclear antigen was significantly lower in the cirrhotic group. CREB, PKA and iPLA2 activities, assessed by western blots and electromobility shift assay, were significantly impaired after hepatectomy in the cirrhosis group. PKA and iPLA2 silencing by siRNA transfection significantly inhibited CREB activity and cell growth in transformed hepatocytes in vitro. Conclusions: CREB dysfunction, mediated by PKA and iPLA2 suppression, may be involved in the deteriorated liver regeneration in the cirrhotic rats.

Original languageEnglish
Pages (from-to)1110-1119
Number of pages10
JournalHepatology Research
Volume41
Issue number11
DOIs
Publication statusPublished - Nov 1 2011

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Calcium-Independent Phospholipase A2
Liver Regeneration
Phospholipases A2
Hepatectomy
Adenosine Monophosphate
Cyclic AMP-Dependent Protein Kinases
Cyclic AMP
Carrier Proteins
Liver
Thioacetamide
Proliferating Cell Nuclear Antigen
Thymidine
Small Interfering RNA
Transfection
Regeneration
Hepatocytes
Fibrosis
Western Blotting
Staining and Labeling
Growth

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Infectious Diseases

Cite this

Impaired activities of cyclic adenosine monophosphate-responsive element binding protein, protein kinase A and calcium-independent phospholipase A2 are involved in deteriorated regeneration of cirrhotic liver after partial hepatectomy in rats. / Zhao, Gang; Wakabayashi, Rie; Shimoda, Shinya; Fukunaga, Yumi; Kumagai, Michiaki; Tanaka, Masao; nakano, kenji.

In: Hepatology Research, Vol. 41, No. 11, 01.11.2011, p. 1110-1119.

Research output: Contribution to journalArticle

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AU - Wakabayashi, Rie

AU - Shimoda, Shinya

AU - Fukunaga, Yumi

AU - Kumagai, Michiaki

AU - Tanaka, Masao

AU - nakano, kenji

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