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char = p;code = 112
char = a;code = 97
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char = g;code = 103
char = ;code = 32
char = R;code = 82
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char = A;code = 65
char = ;code = 32
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char = i;code = 105
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char = c;code = 99
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char = l;code = 108
char = l;code = 108
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char = .;code = 46
result sql = Gallic acid suppresses lipopolysaccharide-induced nuclear factor-kappaB signaling by preventing RelA acetylation in A549 lung cancer cells.
Gallic acid suppresses lipopolysaccharide-induced nuclear factor-kappaB signaling by preventing RelA acetylation in A549 lung cancer cells.
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result sql = Although multiple studies have revealed that gallic acid plays an important role in the inhibition of malignant transformation, cancer development, and inflammation, the molecular mechanism of gallic acid in inflammatory diseases is still unclear. In this study, we identified gallic acid from Rosa rugosa as a histone acetyltransferase (HAT) inhibitor with global specificity for the majority of HAT enzymes, but with no activity toward epigenetic enzymes including sirtuin (silent mating type information regulation 2 homologue) 1 (S. cerevisiae), histone deacetylase, and histone methyltransferase. Enzyme kinetic studies indicated that gallic acid uncompetitively inhibits p300/CBP-dependent HAT activities. We found that gallic acid inhibits p300-induced p65 acetylation, both in vitro and in vivo, increases the level of cytosolic IkappaBalpha, prevents lipopolysaccharide (LPS)-induced p65 translocation to the nucleus, and suppresses LPS-induced nuclear factor-kappaB activation in A549 lung cancer cells. We have also shown that gallic acid treatment inhibits the acetylation of p65 and the LPS-induced serum levels of interleukin-6 in vivo. Importantly, gallic acid generally inhibited inflammatory responses caused by other stimuli, including LPS, IFN-gamma, and interleukin-1beta, and further downregulated the expression of nuclear factor-kappaB-regulated antiapoptotic genes. These results show the crucial role of acetylation in the development of inflammatory diseases.

Publication: Mol. Cancer Res. 2009 Dec ;7(12)::2011-21. :doi: 10.1158/1541-7786.MCR-09-0239.
Publication Date: 2009 Dec
Study Author(s): Choi, Kyung-Chul;Lee, Yoo-Hyun;Jung, Myung Gu;Kwon, Seung Hyun;Kim, Mi-Jeong;Jun, Woo Jin;Lee, Jeongmin;Lee, Jae Myun;Yoon, Ho-Geun;
Institution: Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, 134 Sicnchon-dong, Seodaemun-gu, Seoul 120-752, South Korea.
Shortcut link to this study:
Although multiple studies have revealed that gallic acid plays an important role in the inhibition of malignant transformation, cancer development, and inflammation, the molecular mechanism of gallic acid in inflammatory diseases is still unclear. In this study, we identified gallic acid from Rosa rugosa as a histone acetyltransferase (HAT) inhibitor with global specificity for the majority of HAT enzymes, but with no activity toward epigenetic enzymes including sirtuin (silent mating type information regulation 2 homologue) 1 (S. cerevisiae), histone deacetylase, and histone methyltransferase. Enzyme kinetic studies indicated that gallic acid uncompetitively inhibits p300/CBP-dependent HAT activities. We found that gallic acid inhibits p300-induced p65 acetylation, both in vitro and in vivo, increases the level of cytosolic IkappaBalpha, prevents lipopolysaccharide (LPS)-induced p65 translocation to the nucleus, and suppresses LPS-induced nuclear factor-kappaB activation in A549 lung cancer cells. We have also shown that gallic acid treatment inhibits the acetylation of p65 and the LPS-induced serum levels of interleukin-6 in vivo. Importantly, gallic acid generally inhibited inflammatory responses caused by other stimuli, including LPS, IFN-gamma, and interleukin-1beta, and further downregulated the expression of nuclear factor-kappaB-regulated antiapoptotic genes. These results show the crucial role of acetylation in the development of inflammatory diseases.
PMID: 19996305

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