Gene expression in rat lungs during early response to paraquat-induced oxidative stress

Tomita, Masafumi; Okuyama, Toshiko; Katsuyama, Hironobu; Hidaka, Kazuo; Otsuki, Takemi; Ishikawa, Takaki

doi:10.3892/ijmm.17.1.37

Cited by 13 publications

(14 citation statements)

References 29 publications

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“…A previous study of wide-scale gene expression in response to 1 hr exposure to the oxidative stress inducer, juglone, also showed significant upregulation of transcripts for several GSTs identified in this study [45]. Increased GST expression has previously been observed following paraquat treatment in rodents [49]–[51] and in Drosophila [52]. Our data may indicate that dazomet is a substrate for Phase II metabolism in the absence of prior Phase I metabolism, explaining the induction of Phase II but not Phase I enzymes by this compound.…”

Section: Discussionsupporting

confidence: 78%

Adaptive and Specialised Transcriptional Responses to Xenobiotic Stress in Caenorhabditis elegans Are Regulated by Nuclear Hormone Receptors

et al. 2013

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Characterisation of the pathways by which xenobiotics are metabolised and excreted in both target and non-target organisms is crucial for the rational design of effective and specific novel bioactive molecules. Consequently, we have investigated the induced responses of the model nematode Caenorhabditis elegans to a variety of xenobiotics which represent a range of putative modes of action. The majority of genes that were specifically induced in preliminary microarray analyses encoded enzymes from Phase I and II metabolism, including cytochrome P450s, short chain dehydrogenases, UDP-glucuronosyl transferases and glutathione transferases. Changes in gene expression were confirmed by quantitative PCR and GFP induction in reporter strains driven by promoters for transcription of twelve induced enzymes was investigated. The particular complement of metabolic genes induced was found to be highly contingent on the xenobiotic applied. The known regulators of responses to applied chemicals ahr-1, hif-1, mdt-15 and nhr-8 were not required for any of these inducible responses and skn-1 regulated GFP expression from only two of the promoters. Reporter strains were used in conjunction with systematic RNAi screens to identify transcription factors which drive expression of these genes under xenobiotic exposure. These transcription factors appeared to regulate specific xenobiotic responses and have no reported phenotypes under standard conditions. Focussing on nhr-176 we demonstrate the role of this transcription factor in mediating the resistance to thiabendazole.

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Section: Discussionsupporting

confidence: 78%

Adaptive and Specialised Transcriptional Responses to Xenobiotic Stress in Caenorhabditis elegans Are Regulated by Nuclear Hormone Receptors

et al. 2013

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“…Respiratory failure is a frequent cause of mortality in cases of moderate to severe paraquat poisoning. Certain results indicate that the acclimation to oxidative stress is a highly complex process at the onset of paraquat-induced damage (1,8,21). Mainwaring et al (22) reported that a number of the transcriptional responses to paraquat were rapid, and that the predominant molecular functions and biological processes associated with these genes included membrane transport, oxidative stress, lung development, epithelial cell differentiation and TGF-β1 signaling (22).…”

Section: Discussionmentioning

confidence: 99%

Effect of transforming growth factor-β1 on acute lung injury caused by paraquat

Kan

Jian

Zhou

et al. 2014

Molecular Medicine Reports

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Abstract. In China, and other Asian countries, numerous patients have succumbed to pulmonary fibrosis induced by paquarat poisoning, but the early pathogenesis remains unclear. In this study the effect of cytokine transforming growth factor (TGF)-β1 was observed in early acute paraquat poisoning and examined the mechanism by which paraquat caused early acute lung injury. It was discovered that the rat serum TGF-β1 levels in the paraquat groups were significant higher than that in the control group (P<0.05) and the rat pulmonary TGF-β1 mRNA expression levels were also higher than that in the control group (P<0.05). Histological examination indicated that the rat lung tissue was broad and congested, and had been infiltrated by inflammatory cells. Masson's trichrome staining for collagen showed that the lung tissue appeared fibrotic following paraquat poisoning. Ultramicrostructure observation found that macrophages, red blood cells, lymphocytes and granulocytes infiltrated the alveolar space and there were cytolysosomes in the macrophages. The shape of the type II alveolar epithelial cell nuclei were irregular with karyopyknosis. The heterochromatin migrated to the cell edge and lamellar body vacuolization was also observed. Type I alveolar epithelial cells shrank. In conclusion, the effect of cytokine TGF-β1 on paraquat-induced acute lung tissue injury may be important.

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“…Clark et al reported similar histological effects of PQ in rats, mice and dogs (2) in which the lung, liver, kidney and thymus were affected, with the lung being the major target. In forensic practice, fatal cases of acute PQ poisoning are often encountered (3). PQ-induced pulmonary toxicity is known to result in pulmonary edema, infiltration of inflammatory cells and damage to the alveolar epithelium, which may progress to severe fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Unbalanced MMP/TIMP-1 expression during the development of experimental pulmonary fibrosis with acute paraquat poisoning

Wang

et al. 2011

Mol Med Rep

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Abstract. Paraquat (PQ)-induced pulmonary toxicity is known to result in pulmonary edema, infiltration of inflammatory cells and damage to the alveolar epithelium, which may progress to severe fibrosis. Matrix metalloproteinases (MMPs) and their physiological inhibitors, tissue inhibitors of matrix metalloproteinases (TIMPs), which degrade and remodel the excess extracellular matrix, are believed to play an important role in the development of fibrotic tissue. In this study, we examined the sequential expression of MMP-2, MMP-9 and TIMP-1 in a rat model of pulmonary fibrosis induced by PQ. Adult male Sprague-Dawley rats were treated intraperitoneally with PQ (20 mg/kg) and saline (control group). Rats were sacrificed at days 1, 3, 7 and 21 after the PQ treatment. Lungs were excised for histological evaluation and immunohistochemical analyses, as well as the determination of collagen content, gene expression by fluorimeter-based quantitive RT-PCR assay and gelatinolytic activity by zymography. Lung MMP-2 and -9 mRNA expression progressively increased and reached a peak on day 7 after PQ treatment, while TiMP-1 mrna levels in the PQ-treated lungs reached a peak on day 21 after modeling. Lung zymography revealed an increase in progelatinase B, progelatinase a and their active forms. In conclusion, unbalanced MMP/TIMP-1 expression and excessive gelatinolytic activity contribute to PQ-induced pulmonary fibrosis. Their precise role should be studied in depth as they may represent relevant therapeutic targets for PQ poisoning-induced pulmonary fibrosis.

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Gene expression in rat lungs during early response to paraquat-induced oxidative stress

Cited by 13 publications

References 29 publications

Adaptive and Specialised Transcriptional Responses to Xenobiotic Stress in Caenorhabditis elegans Are Regulated by Nuclear Hormone Receptors

Adaptive and Specialised Transcriptional Responses to Xenobiotic Stress in Caenorhabditis elegans Are Regulated by Nuclear Hormone Receptors

Effect of transforming growth factor-β1 on acute lung injury caused by paraquat

Unbalanced MMP/TIMP-1 expression during the development of experimental pulmonary fibrosis with acute paraquat poisoning

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