Mechanisms of induction of cytosolic and microsomal glutathione transferase (GST) genes by xenobiotics and pro-inflammatory agents

TY - JOUR

T1 - Mechanisms of induction of cytosolic and microsomal glutathione transferase (GST) genes by xenobiotics and pro-inflammatory agents

A1 - Higgins,Larry G.

A1 - Hayes,John D.

AU - Higgins,Larry G.

AU - Hayes,John D.

PY - 2011/5

Y1 - 2011/5

N2 - <p>Glutathione transferase (GST) isoezymes are encoded by three separate families of genes (designated cytosolic, microsomal and mitochondrial transferases), with distinct evolutionary origins, that provide mammalian species with protection against electrophiles and oxidative stressors in the environment. Members of the cytosolic class Alpha, Mu, Pi and Theta GST, and also certain microsomal transferases (MGST2 and MGST3), are up-regulated by a diverse spectrum of foreign compounds typified by phenobarbital, 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, pregnenolone-16 alpha-carbonitrile, 3-methylcholanthrene, 2,3,7,8-tetrachloro-dibenzo-p-dioxin, beta-naphthoflavone, butylated hydroxyanisole, ethoxyquin, oltipraz, fumaric acid, sulforaphane, coumarin, 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole, 12-O-tetradecanoylphorbol-13-acetate, dexamethasone and thiazolidinediones. Collectively, these compounds induce gene expression through the constitutive androstane receptor (CAR), the pregnane X receptor (PXR), the aryl hydrocarbon receptor (AhR), NF-E2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor-gamma (PPAR gamma) and CAATT/enhancer binding protein (C/EBP) beta. The microsomal T family includes 5-lipoxygenase activating protein (FLAP), leukotriene C-4 synthase (LTC4S) and prostaglandin E-2 synthase (PGES-1), and these are up-regulated by tumour necrosis factor-alpha, lipopolysaccharide and transforming growth factor-beta. Induction of genes encoding FLAP, LTC4S and PGES-1 is mediated by the transcription factors C/EBP alpha, C/EBP delta, C/EBP epsilon, nuclear factor-kappa B and early growth response-1. In this article we have reviewed the literature describing the mechanisms by which cytosolic and microsomal GST are up-regulated by xenobiotics, drugs, cytokines and endotoxin. We discuss cross-talk between the different induction mechanisms, and have employed bioinformatics to identify cis-elements in the upstream regions of GST genes to which the various transcription factors mentioned above may be recruited.</p>

AB - <p>Glutathione transferase (GST) isoezymes are encoded by three separate families of genes (designated cytosolic, microsomal and mitochondrial transferases), with distinct evolutionary origins, that provide mammalian species with protection against electrophiles and oxidative stressors in the environment. Members of the cytosolic class Alpha, Mu, Pi and Theta GST, and also certain microsomal transferases (MGST2 and MGST3), are up-regulated by a diverse spectrum of foreign compounds typified by phenobarbital, 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, pregnenolone-16 alpha-carbonitrile, 3-methylcholanthrene, 2,3,7,8-tetrachloro-dibenzo-p-dioxin, beta-naphthoflavone, butylated hydroxyanisole, ethoxyquin, oltipraz, fumaric acid, sulforaphane, coumarin, 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole, 12-O-tetradecanoylphorbol-13-acetate, dexamethasone and thiazolidinediones. Collectively, these compounds induce gene expression through the constitutive androstane receptor (CAR), the pregnane X receptor (PXR), the aryl hydrocarbon receptor (AhR), NF-E2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor-gamma (PPAR gamma) and CAATT/enhancer binding protein (C/EBP) beta. The microsomal T family includes 5-lipoxygenase activating protein (FLAP), leukotriene C-4 synthase (LTC4S) and prostaglandin E-2 synthase (PGES-1), and these are up-regulated by tumour necrosis factor-alpha, lipopolysaccharide and transforming growth factor-beta. Induction of genes encoding FLAP, LTC4S and PGES-1 is mediated by the transcription factors C/EBP alpha, C/EBP delta, C/EBP epsilon, nuclear factor-kappa B and early growth response-1. In this article we have reviewed the literature describing the mechanisms by which cytosolic and microsomal GST are up-regulated by xenobiotics, drugs, cytokines and endotoxin. We discuss cross-talk between the different induction mechanisms, and have employed bioinformatics to identify cis-elements in the upstream regions of GST genes to which the various transcription factors mentioned above may be recruited.</p>

KW - ARE (Antioxidant Response Element)

KW - tBHQ (tert-butylhydroquinone)

KW - CAR (Constitutive Androstane Receptor)

KW - Chemoprevention

KW - EpRE (Electrophile Response Element)

KW - GPEI (Glutathione transferase P Enhancer I)

KW - GRE (Glucocorticoid Response Element)

KW - GSH (reduced glutathione)

KW - Keap1 (Kelch-like ECH-associated protein 1)

KW - PBREM (Phenobarbital-Responsive Enhancer Module)

KW - XRE (Xenobiotic Response Element)

KW - Nrf2 (NF-E2-related factor 2)

KW - AhR (Aryl hydrocarbon Receptor)

KW - LEUKOTRIENE C-4 SYNTHASE

KW - ANTIOXIDANT RESPONSE ELEMENT

KW - TRANSCRIPTION FACTOR NRF2

KW - ARYL-HYDROCARBON RECEPTOR

KW - PREGNANE-X-RECEPTOR

KW - RAT-LIVER CYTOSOL

KW - YA-SUBUNIT GENE

KW - PROSTAGLANDIN-E SYNTHASE-1

KW - CONSTITUTIVE ANDROSTANE RECEPTOR

KW - PROTEIN-KINASE-C

U2 - 10.3109/03602532.2011.567391

DO - 10.3109/03602532.2011.567391

M1 - Scientific review

JO - Drug Metabolism Reviews

JF - Drug Metabolism Reviews

SN - 0360-2532

IS - 2

VL - 43

SP - 92

EP - 137

ER -