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ATP loss and purinergic receptor signaling contribute to early transcriptional responses activated by JNK in liver regeneration after partial hepatectomy in the rat
Author(s) -
Juskeviciute Egle,
Crumm Sara,
Correnti Jason,
Hoek Jan B.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.749.7
Subject(s) - purinergic receptor , microbiology and biotechnology , liver regeneration , biology , signal transduction , kinase , purinergic signalling , receptor , chemistry , regeneration (biology) , biochemistry , adenosine receptor , extracellular , agonist
A complex program of gene expression changes drives the onset of liver regeneration after 70% partial hepatectomy (PHx) in the rat. However, the signals that initiate this response have not been well characterized. We reported recently (Crumm et al., 2008) that a rapid loss of adenine nucleotides (AdN) after PHx generates early stress signals that contribute to the onset of liver regeneration. Conditions that prevent the loss of AdN or that inhibit purinergic receptor activation suppress early signaling responses. This study focuses on the potential role of connexin (Cx) hemi‐channels in AdN loss and downstream signaling events. To specifically block different Cx isoforms, we used gap peptides. Pretreating animals with gap peptide specific for Cx26/32, but not for Cx43 or pannexin‐1 inhibited AdN loss. Pretreatment with the nitric oxide synthase inhibitor L‐NAME or the alpha‐adrenergic antagonist phentolamine also completely prevents loss of and upon PHx. However, pretreatment with the purinergic receptor antagonist suramin does not prevent AdN loss. All these treatments suppress Jun N‐terminal kinase (JNK) phosphorylation after PHx. In the analysis of downstream targets of JNK contributing to the early gene expression changes after PHx these inhibitors also decreased phospho‐cJun transcriptional activity at AP1 and CREB binding sites. Supported by NIH AA008714 /AA018873 to JBH.