Immunohistological Analysis of Glutathione Transferase A4 Distribution in Several Human Tissues Using a Specific Polyclonal Antibody

Desmots, Fabienne; Rissel, Mary; Loyer, Pascal; Turlin, Bruno; Guillouzo, André

doi:10.1177/002215540104901211

Cited by 41 publications

(27 citation statements)

References 28 publications

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“…Interestingly the GSTM1 mRNA level was down-regulated after gentamicin treatment in this study. Downregulation of GSTM1 mRNA was also described in a study comparing gene expression patterns of GSTs in kidney and liver of iron-overloaded mice (Desmots et al, 2001) which indicates a relation between GSTM1 mRNA down-regulation and general oxidative stress mechanisms in kidney.…”

Section: Nephrotoxicitymentioning

confidence: 83%

Identification of genes involved in gentamicin-induced nephrotoxicity in rats – A toxicogenomic investigation

Matheis

Gamber

et al. 2010

Experimental and Toxicologic Pathology

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To cite this version:N. Ozaki, K.A. Matheis, M. Gamber, T. Feidl, T. Nolte, et al.. Identification of genes involved in gentamicin induced nephrotoxicity in rats-a toxicogenomic investigation. Experimental and Toxicologic Pathology, Elsevier, 2010, 62 (5) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d m a n u s c r i p t

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Section: Nephrotoxicitymentioning

confidence: 83%

Identification of genes involved in gentamicin-induced nephrotoxicity in rats – A toxicogenomic investigation

Matheis

Gamber

et al. 2010

Experimental and Toxicologic Pathology

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“…Antibodies-The rabbit polyclonal antibody against a mGSTA4 peptide was characterized in our laboratory (30). The other antibodies were purchased as follows: rabbit polyclonal anti-human GSTA1, GSTMu, and GSTPi antisera from Biotrin, Dublin, Ireland; rabbit polyclonal anti-cytochrome c from Santa Cruz Biotechnology, Santa Cruz, CA; monoclonal anti-cytochrome c oxidase from Molecular Probes, Eugene, OR; monoclonal anti-phospho-p44/42 MAPK (Thr-202/Tyr-204) and polyclonal anti-p44/42 MAPK from Cell Signaling Technology, Beverly, MA; anti-phosphorylated-AKT (Ser-473) from New England Biolabs, Beverly, MA; and anti-albumin from ICN Pharmaceuticals, Orsay, France; horseradish peroxidase-linked rabbit antiserum from Bio-Rad, Ivry sur Seine, France; and mouse and goat anti-rabbit rhodamineconjugated IgG from Santa Cruz Biotechnology.…”

Section: Methodsmentioning

confidence: 99%

Pro-inflammatory Cytokines Tumor Necrosis Factor α and Interleukin-6 and Survival Factor Epidermal Growth Factor Positively Regulate the Murine GSTA4 Enzyme in Hepatocytes

Desmots¹,

Rissel²,

Gilot³

et al. 2002

Journal of Biological Chemistry

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We hypothesized that glutathione transferases could be induced and may participate to cellular defenses against the oxidative stress occurring during liver regeneration. Here, we evidenced that murine GSTA1 (mGSTA1), A4, Pi, and Mu are up-regulated during mouse liver regeneration, exhibiting a biphasic pattern of induction correlating early G 1 phase and G 1 /S transition of the cell cycle. Using confocal microscopy immunolocalization and subcellular fractionation, mGSTA4 was demonstrated in both mitochondria and cytosol and found preferentially increased in cytosol during liver regeneration. In addition, mGSTA4 was induced in vivo and in cultured hepatocytes by tumor necrosis factor ␣ (TNF␣), interleukin-6 (IL-6), and epidermal growth factor (EGF), factors that play crucial roles in hepatocyte survival and proliferation during liver regeneration. However, the mitogenic effect of EGF was not responsible for the induction of mGSTA4. In transient transfections, IL-6 and EGF, but not TNF␣, transactivated the human GSTA4 (hGSTA4) promoter cloned upstream of the luciferase reporter gene suggesting that IL-6 and EGF up-regulated hGSTA4 at a transcriptional level, whereas TNF␣ could rather act at a post-transcriptional level. The inhibition of phosphoinositide 3-kinase, p38 MAPK, and MEK/ERK signaling pathways, using specific inhibitors, prevented EGF-dependent induction of mGSTA4 and transactivation of hGSTA4 promoter. Altogether, these data favor the conclusion that, in regenerating hepatocytes, several GST isoforms are induced and that cytokines TNF␣ and IL-6 and survival factor EGF positively regulate mGSTA4 via survival signaling pathways. Quiescent, differentiated hepatocytes are able to re-enter the cell cycle and proliferate to restore the liver mass following liver deficits resulting from surgical removal or caused by chemicals and viruses. Entry into and progression through early G 1 phase of the cell cycle, also called priming (1), are induced by the cytokines tumor necrosis factor ␣ (TNF␣) 1 (2, 3) and interleukin-6 (IL-6) (4) and are required for the hepatocytes to fully respond to growth factors (3). TNF␣ binding to its type 1 receptor successively activates NF B (5), IL-6 expression, and STAT3 (6, 7) in the early G 1 phase, which constitute a key signaling pathway during hepatocyte proliferation (4, 8). The late G 1 progression and commitment to DNA replication are controlled by growth factors (9 -11) including hepatocyte growth factor, transforming growth factor-␣, and epidermal growth factor (EGF) (1) through the activation of the MEK/ ERK pathway (11).Several lines of evidence indicate that partial hepatectomy (PH) is rapidly followed by an oxidative stress due to increased reactive oxygen species (ROS) and nitric oxide (NO) production leading to lipid peroxidation (12)(13)(14).Regarding ROS, TNF␣ is now recognized as playing a crucial role in the production of these species during liver regeneration. In support of such a role, it is worth noting that the multimerization of TNF␣ type I receptor follow...

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“…Previously, glutathione transferase alpha 4 (GSTA4-4) was shown to be abundantly expressed in protein extracts from whole mouse hearts (23) and to be localized within both the mitochondria and cytosol of mouse liver cells (24). A study of the human heart showed uniform staining of cardiomyocytes with a GSTA4-4 antibody (25). …”

Section: Introductionmentioning

confidence: 99%

Protection from Oxidative and Electrophilic Stress in the Gsta4-null Mouse Heart

et al. 2013

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4-hydroxynonenal (4-HNE) mediates many pathological effects of oxidative and electrophilic stress and signals to activate cytoprotective gene expression regulated by NF-E2-related factor 2 (Nrf2). By exhibiting very high levels of 4-HNE-conjugating activity, the murine glutathione transferase alpha 4 (GSTA4-4) helps regulate cellular 4-HNE levels. To examine the role of 4-HNE in vivo, we disrupted the murine Gsta4 gene. Gsta4-null mice exhibited no cardiac phenotype under normal conditions and no difference in cardiac 4-HNE level as compared to wild-type (WT) mice. We hypothesized that the Nrf2 pathway might contribute an important compensatory mechanism to remove excess cardiac 4-HNE in Gsta4-null mice. Cardiac nuclear extracts from Gsta4-null mice exhibited significantly higher Nrf2 binding to antioxidant-response elements (AREs). We also observed responses in critical Nrf2 target gene products: elevated Sod2, Cat, and Akr1b7 mRNA levels and significant increases in both cardiac anti-oxidant and anti-electrophile enzyme activities. Gsta4-null mice were less sensitive and maintained normal cardiac function following chronic doxorubicin (DOX) treatment, known to increase cardiac 4-HNE levels. Hence, in the absence of GSTA4-4 to modulate both physiological and pathological 4-HNE levels, the adaptive Nrf2 pathway may be primed to contribute to a preconditioned cardiac phenotype in the Gsta4-null mouse.

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Immunohistological Analysis of Glutathione Transferase A4 Distribution in Several Human Tissues Using a Specific Polyclonal Antibody

Cited by 41 publications

References 28 publications

Identification of genes involved in gentamicin-induced nephrotoxicity in rats – A toxicogenomic investigation

Identification of genes involved in gentamicin-induced nephrotoxicity in rats – A toxicogenomic investigation

Pro-inflammatory Cytokines Tumor Necrosis Factor α and Interleukin-6 and Survival Factor Epidermal Growth Factor Positively Regulate the Murine GSTA4 Enzyme in Hepatocytes

Protection from Oxidative and Electrophilic Stress in the Gsta4-null Mouse Heart

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