Gene interactions and pathways from curated databases and text-mining
J Pharmacol Exp Ther 2006, PMID: 16293713

Identification of the insulin signaling cascade in the regulation of alpha-class glutathione S-transferase expression in primary cultured rat hepatocytes.

Kim, Sang K; Abdelmegeed, Mohamed A; Novak, Raymond F

We reported previously that insulin elevated alpha-class glutathione S-transferase (GSTs) protein levels in primary cultured rat hepatocytes (Kim et al., 2003b). In contrast, glucagon down-regulated alpha- and pi-class GST expression, and mechanistic research implicated cAMP and protein kinase A in this process (Kim et al., 2003b). The present study examines the signaling pathways involved in the regulation of alpha-class GST in response to insulin in primary cultured rat hepatocytes. Protein levels of GSTA1/2 and GSTA3/5 and activity of GST toward 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD) were increased in an insulin concentration-dependent manner. Treatment of cells with the phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one] or rapamycin, an inhibitor of mammalian target of rapamycin and ribosomal p70 S6 kinase (p70S6K) phosphorylation, or with an adenovirus containing green fluorescent protein and a dominant-negative and kinase-dead Akt, effectively inhibited the insulin-mediated increase in alpha-class GST expression and GST activity toward NBD. In contrast, PD98059 (2'-amino-3'-methoxyflavone), an inhibitor of mitogen-activated protein kinase kinase, SP600125 (1,9-pyrazoloanthrone), an inhibitor of c-Jun N-terminal kinase, SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imadazole], an inhibitor of p38 mitogen-activated protein kinase, or bisindolylmaleimide, a broad spectrum inhibitor of protein kinase C, did not inhibit the insulin-mediated increase in alpha-class GST protein levels in hepatocytes. These results show that PI3K/Akt/p70S6K signaling is active in the insulin-mediated up-regulation of the antioxidant defense system and that low insulin levels, as encountered in diabetes, potentially increase the susceptibility of hepatocytes to xenobiotic-mediated and/or oxidative stress-mediated damage.

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Text Mining Data

GST → insulin: " The present study examines the signaling pathways involved in the regulation of alpha-class GST in response to insulin in primary cultured rat hepatocytes "

GST → insulin: " Treatment of cells with the phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY294002 [ 2- ( 4-morpholinyl ) -8-phenyl-4H-1-benzopyran-4-one ] or rapamycin, an inhibitor of mammalian target of rapamycin and ribosomal p70 S6 kinase (p70S6K) phosphorylation, or with an adenovirus containing green fluorescent protein and a dominant negative and kinase-dead Akt, effectively inhibited the insulin mediated increase in alpha-class GST expression and GST activity toward NBD "

mammalian target of rapamycin → phosphatidylinositol 3-kinase (PI3K): " Treatment of cells with the phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY294002 [ 2- ( 4-morpholinyl ) -8-phenyl-4H-1-benzopyran-4-one ] or rapamycin, an inhibitor of mammalian target of rapamycin and ribosomal p70 S6 kinase (p70S6K) phosphorylation, or with an adenovirus containing green fluorescent protein and a dominant negative and kinase-dead Akt, effectively inhibited the insulin mediated increase in alpha-class GST expression and GST activity toward NBD "

p70 S6 kinase (p70S6K) → phosphatidylinositol 3-kinase (PI3K): " Treatment of cells with the phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY294002 [ 2- ( 4-morpholinyl ) -8-phenyl-4H-1-benzopyran-4-one ] or rapamycin, an inhibitor of mammalian target of rapamycin and ribosomal p70 S6 kinase (p70S6K) phosphorylation, or with an adenovirus containing green fluorescent protein and a dominant negative and kinase-dead Akt, effectively inhibited the insulin mediated increase in alpha-class GST expression and GST activity toward NBD "

GST → insulin: " In contrast, PD98059 ( 2'-amino-3'-methoxyflavone ), an inhibitor of mitogen activated protein kinase kinase, SP600125 ( 1,9-pyrazoloanthrone ), an inhibitor of c-Jun N-terminal kinase, SB203580 [ 4- ( 4-fluorophenyl ) -2- ( 4-methylsulfinylphenyl ) -5- ( 4-pyridyl ) 1H-imadazole ], an inhibitor of p38 mitogen activated protein kinase, or bisindolylmaleimide, a broad spectrum inhibitor of protein kinase C, did not inhibit the insulin mediated increase in alpha-class GST protein levels in hepatocytes "

PI3K/Akt/p70S6K → insulin: " These results show that PI3K/Akt/p70S6K signaling is active in the insulin mediated up-regulation of the antioxidant defense system and that low insulin levels, as encountered in diabetes, potentially increase the susceptibility of hepatocytes to xenobiotic mediated and/or oxidative stress mediated damage "

PI3K/Akt/p70S6K → insulin: " These results show that PI3K/Akt/p70S6K signaling is active in the insulin mediated up-regulation of the antioxidant defense system and that low insulin levels, as encountered in diabetes, potentially increase the susceptibility of hepatocytes to xenobiotic mediated and/or oxidative stress mediated damage "

insulin → PI3K/Akt/p70S6K: " These results show that PI3K/Akt/p70S6K signaling is active in the insulin mediated up-regulation of the antioxidant defense system and that low insulin levels, as encountered in diabetes, potentially increase the susceptibility of hepatocytes to xenobiotic mediated and/or oxidative stress mediated damage "

Manually curated Databases

No curated data.