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Regulation of arginase‐1 expression in macrophages by a protein kinase a type I and histone deacetylase dependent pathway
Author(s) -
Haffner Ivonne,
Teupser Daniel,
Holdt Lesca M.,
Ernst Jana,
Burkhardt Ralph,
Thiery Joachim
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21422
Subject(s) - trichostatin a , histone deacetylase , arginase , acetylation , chemistry , hdac4 , microbiology and biotechnology , histone , histone deacetylase 2 , protein kinase a , hdac10 , histone deacetylase 5 , kinase , biology , biochemistry , gene , amino acid , arginine
The aim of the current study was to investigate the cAMP‐dependent regulation of arginase‐1 (ARG1) expression in RAW‐macrophages. Basal ARG1 mRNA expression was low and increased upon incubation with the cAMP analogue Br‐cAMP. We used selective agonists of protein kinase A type I (PKAI), type II (PKAII) and exchange protein directly activated by cAMP (EPAC) to determine the pathway responsible for ARG1 expression. Activation of PKAI led to a significant up‐regulation of ARG1 mRNA expression and arginase enzyme activity. In contrast, neither activation of PKAII nor activation of EPAC affected ARG1 expression. In addition, it has been shown that histone deacetylase (HDAC) activity plays a critical role in cAMP‐dependent transcriptional regulation. Incubation with Br‐cAMP and the HDAC inhibitor trichostatin A (TSA) led to a concentration‐dependent suppression of ARG1 expression. These data indicate that cAMP‐dependent activation of ARG1 expression is mediated by PKAI and requires histone deacetylation. J. Cell. Biochem. 103: 520–527, 2008. © 2007 Wiley‐Liss, Inc.