Paraquat-Induced Oxidative Stress and Dysfunction of the Glutathione Redox Cycle in Pulmonary Microvascular Endothelial Cells

Tsukamoto, Masako; Tampo, Yoshiko; Sawada, Minoru; Yonaha, Masanori

doi:10.1006/taap.2001.9325

Cited by 69 publications

(59 citation statements)

References 57 publications

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“…Free radicals are known to play a crucial role in PQ-induced lung toxicity (Tampo et al, 1999;Minakata et al, 2000;Kim et al, 2010). It has been reported that the toxicity is related to redox cycling of an iron-PQ complex, which in turn catalyzes the formation of ROS with the ultimate progression of lipid peroxidation (Tsukamoto et al, 2002;Gil et al, 2007). In this study, PC reduced the acute lung injury induced by PQ intoxication, and the MDA concentration, as a marker of lipid peroxidation, was lower in the PQ + PC-treated group than in the PQ-treated group.…”

Section: Discussionmentioning

confidence: 99%

The protective effect of C-phycocyanin on paraquat-induced acute lung injury in rats

Sun

Zhang²,

Yan³

et al. 2011

Environmental Toxicology and Pharmacology

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Section: Discussionmentioning

confidence: 99%

The protective effect of C-phycocyanin on paraquat-induced acute lung injury in rats

Sun

Zhang²,

Yan³

et al. 2011

Environmental Toxicology and Pharmacology

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“…in systems ranging from isolated mitochondria (12-15) and cultured mammalian cells (4,14,16,17), to whole organisms including Saccharomyces cerevisiae (18 -21), Caenorhabditis elegans (22, 23), Drosophila melanogaster (9, 24 -26), and rodents (6,11,27). In many of these studies, PQ increases mitochondrial oxidative damage; for example, mitochondrial expression of human peroxiredoxin 5 protects yeast more effectively against PQ toxicity than expression in the cytosol (19); flies overexpressing catalase in mitochondria are resistant to PQ, whereas enhancement of cytosolic catalase was not protective (24); RNA interference silencing of MnSOD (the isoform of superoxide dismutase located in the mitochondrial matrix) in flies causes hypersensitivity to PQ (9), mice heterozygous for MnSOD show greater sensitivity to PQ than wild-type (11), and mitochondrial swelling is one of the earliest ultrastructural changes upon PQ exposure in vivo (28,29).…”

mentioning

confidence: 99%

Complex I Is the Major Site of Mitochondrial Superoxide Production by Paraquat

Cochemé

Murphy

2008

Journal of Biological Chemistry

509

375

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Paraquat (1,1-dimethyl-4,4-bipyridinium dichloride) is widely used as a redox cycler to stimulate superoxide production in organisms, cells, and mitochondria. This superoxide production causes extensive mitochondrial oxidative damage, however, there is considerable uncertainty over the mitochondrial sites of paraquat reduction and superoxide formation. Here we show that in yeast and mammalian mitochondria, superoxide production by paraquat occurs in the mitochondrial matrix, as inferred from manganese superoxide dismutase-sensitive mitochondrial DNA damage, as well as from superoxide assays in isolated mitochondria, which were unaffected by exogenous superoxide dismutase. This paraquat-induced superoxide production in the mitochondrial matrix required a membrane potential that was essential for paraquat uptake into mitochondria. This uptake was of the paraquat dication, not the radical monocation, and was carrier-mediated. Experiments with disrupted mitochondria showed that once in the matrix paraquat was principally reduced by complex I (mammals) or by NADPH dehydrogenases (yeast) to form the paraquat radical cation that then reacted with oxygen to form superoxide. Together this membrane potential-dependent uptake across the mitochondrial inner membrane and the subsequent rapid reduction to the paraquat radical cation explain the toxicity of paraquat to mitochondria.Paraquat (1,1Ј-dimethyl-4,4Ј-bipyridinium dichloride; PQ) 2 is used to increase superoxide (O 2 . ) flux when investigating oxidative stress (reviewed in Refs. 1 and 2). The paraquat dication (PQ 2ϩ ) accepts an electron from a reductant to form the paraquat monocation radical (PQ . . and regenerate PQ 2ϩ (Fig. 1A). This redox cycling is a proximal cause of PQ toxicity, as indicated by the protection against PQ by superoxide dismutase (SOD) overexpression or administration of SOD mimetics (4 -8), and by the PQ hypersensitivity caused by SOD deficiency (9 -11).PQ has been used to generate O 2 . in systems ranging from isolated mitochondria (12-15) and cultured mammalian cells (4,14,16,17), to whole organisms including Saccharomyces cerevisiae (18 -21), Caenorhabditis elegans (22, 23), Drosophila melanogaster (9, 24 -26), and rodents (6,11,27). In many of these studies, PQ increases mitochondrial oxidative damage; for example, mitochondrial expression of human peroxiredoxin 5 protects yeast more effectively against PQ toxicity than expression in the cytosol (19); flies overexpressing catalase in mitochondria are resistant to PQ, whereas enhancement of cytosolic catalase was not protective (24); RNA interference silencing of MnSOD (the isoform of superoxide dismutase located in the mitochondrial matrix) in flies causes hypersensitivity to PQ (9), mice heterozygous for MnSOD show greater sensitivity to PQ than wild-type (11), and mitochondrial swelling is one of the earliest ultrastructural changes upon PQ exposure in vivo (28,29). Therefore the interaction of PQ with mitochondria is an important component of its toxicity, and PQ is used in expe...

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“…23,24) After treating Schwann cells with GA, the fluorescence intensity of hydroethidine and aconitase activity were measured as described previously. 25,26) Measurement of γ-Glutamylcysteine Synthetase (γ-GCS) and Nuclear Factor E2-Related Factor 2 (Nrf2) mRNA Levels Quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis was used to measure γ-GCS mRNA and Nrf2 mRNA levels. Total RNA from treated cells was extracted with RNAspin Mini (GE Healthcare) according to the manufacturer's protocol.…”

Section: Methodsmentioning

confidence: 99%

“…26) Protein concentrations were determined using the Bradford method with bovine serum albumin as the standard.…”

Section: Methodsmentioning

confidence: 99%

Glycolaldehyde Induces Cytotoxicity and Increases Glutathione and Multidrug-Resistance-Associated Protein Levels in Schwann Cells

Sato

Tatsunami

Yama

et al. 2013

Biological & Pharmaceutical Bulletin

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Schwann cell injury is observed in diabetic neuropathy. It is speculated that glycolaldehyde (GA), a precursor of advanced glycation end products (AGEs), contributes to the pathogenesis and development of diabetic neuropathy. Here, we demonstrated for the first time that GA at near-physiological concentration decreased the viability of rat Schwann cells. In contrast, methylglyoxal, glyoxal, and 3-deoxyglucosone, all of which are AGE precursors, had no effects on cell viability. It is well known that methylglyoxal causes oxidative damage. In the present study, however, GA failed to induce reactive oxygen species production in Schwann cells. The addition of glutathione (GSH) or N-acetyl-l-cysteine protected Schwann cells from the loss of viability induced by GA. Moreover, GA increased intracellular GSH level and γ-glutamylcysteine synthetase mRNA level. Flow cytometric analysis revealed that GA increased multidrug-resistance-associated protein 1 (MRP1) level as well. Moreover, we demonstrated that the knockdown of MRP1 with small interfering RNA (siRNA) enhanced the loss of cell viability induced by GA. Taken together, these findings suggest that MRP1, together with GSH, plays an important role in the GA-induced toxicity in Schwann cells.

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Paraquat-Induced Oxidative Stress and Dysfunction of the Glutathione Redox Cycle in Pulmonary Microvascular Endothelial Cells

Cited by 69 publications

References 57 publications

The protective effect of C-phycocyanin on paraquat-induced acute lung injury in rats

The protective effect of C-phycocyanin on paraquat-induced acute lung injury in rats

Complex I Is the Major Site of Mitochondrial Superoxide Production by Paraquat

Glycolaldehyde Induces Cytotoxicity and Increases Glutathione and Multidrug-Resistance-Associated Protein Levels in Schwann Cells

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