Premium
Ischemia‐Reperfusion‐Inducible Protein Modulates the Activity of Metabolizing Enzymes
Author(s) -
Obianom Obinna,
Shu Yan
Publication year - 2015
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.29.1_supplement.lb524
Subject(s) - glutathione , glutathione s transferase , cytochrome p450 , microbiology and biotechnology , biochemistry , isozyme , biology , complementary dna , aldehyde dehydrogenase , gpx1 , gene expression , chemistry , enzyme , gene , glutathione peroxidase
Ischemia‐Reperfusion‐Inducible Protein (IRIP) belongs to the SUA5/YrdC/YciO protein family. Alterations in this protein have been shown previously to affect the gene expression and activity of various drug transporters via posttranscriptional mechanisms yet to be fully unraveled. Herein, we further evaluate the effect of IRIP on metabolizing enzymes. Microarray study was performed using cDNA obtained from liver tissues of liver specific IRIP knockout and wild‐type mice. We identified several metabolic genes, which were significantly changed in knockout mice compared to wild‐type mice.Locus ID Gene Symbol Gene Description P‐value Fold Change 13088 CYP2B10 cytochrome P450 4.74E‐03 2.17 13087 CYP2A5 cytochrome P450 6.37E‐03 0.42 11761 AOX1 aldehyde oxidase 1 5.27E‐03 0.42 14859 GSTA3 glutathione s‐ transferase 5.59E‐03 0.40 13096 CYP2C37 cytochrome P450 7.53E‐03 0.37 14858 GSTA2 glutathione s‐transferase 4.52E‐03 0.37 56615 MGST1 microsomal glutathione s‐transferase 1 9.80E‐04 0.32 71773 UGT2B1 RIKEN cDNA 1300012D20 gene 1.74E‐03 0.30 14857 GSTA1 glutathione s‐transferase 7.10E‐04 0.29 14859 GSTA3 glutathione s‐transferase 1.00E‐04 0.26 14860 GSTA4 glutathione s‐transferase 8.30E‐04 0.25 66447 MGST3 microsomal glutathione s‐transferase 3 1.10E‐04 0.23 11522 ADH1 alcohol dehydrogenase 2.71E‐03 0.17Subsequent studies using western blots, RT‐qPCRand activity assays especially focusing on microsomal and cytosolic glutathione‐s‐transferases and alcohol dehydrogenases were performed. At the mRNA expression level, several genes including glutathione‐s‐transferases (GST) were upregulated, while their protein levels were significantly down‐regulated. GST activity assay measured by 1‐chloro‐2, 4‐dinitrobenzene metabolism showed a decreased GST activity in knockout mice compared to wild‐type littermates.These findings suggest that IRIP can modulate the expression of some key metabolizing enzymes in the liver in addition to already identified transporters through a mechanism consistent with posttranscriptional modifications, with potential implications in the disposition and metabolism of endobiotics and xenobiotics.