Expression of catalase and glutathione peroxidase in renal insufficiency

Sindhu, Ram K.; Ehdaie, Ashkan; Farmand, Farbod; Dhaliwal, Kanwaljit K.; Nguyen, Tri Q.; Chen, Zhan; Roberts, Christian K.; Vaziri, Nosratola D.

doi:10.1016/j.bbamcr.2004.08.013

Cited by 68 publications

(48 citation statements)

References 29 publications

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“…Major enzymatic antioxidants found in vascular tissue include SOD, catalase, glutathione peroxidases, thioredoxin and peroxiredoxin. 114,115 Non-enzymatic antioxidants include ascorbate, tocopherols, glutathione, bilirubin and uric acid and scavenge OH and other free radicals. 116 Extracellular SOD, the major vascular SOD, is produced and secreted by vascular smooth muscle cells and binds to glycosaminoglycans in the vascular extracellular matrix and regulates oxidant status in the vascular interstitium.…”

Section: Vascular Antioxidant Systemsmentioning

confidence: 99%

“…116 Extracellular SOD, the major vascular SOD, is produced and secreted by vascular smooth muscle cells and binds to glycosaminoglycans in the vascular extracellular matrix and regulates oxidant status in the vascular interstitium. 114,115 Decreased antioxidant capacity promotes cellular oxidative stress and has been implicated in cardiovascular and renal oxidative damage associated with hypertension. 114 Activity of SOD, catalase and glutathione (GSH) peroxidase is lower and the glutathione disulfide (GSSG)/GSH is higher in plasma and circulating cells from hypertensive patients than normotensive subjects.…”

Section: Vascular Antioxidant Systemsmentioning

confidence: 99%

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Reactive oxygen species and vascular biology: implications in human hypertension

2010

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Increased vascular production of reactive oxygen species (ROS; termed oxidative stress) has been implicated in various chronic diseases, including hypertension. Oxidative stress is both a cause and a consequence of hypertension. Although oxidative injury may not be the sole etiology, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors. Oxidative stress is a multisystem phenomenon in hypertension and involves the heart, kidneys, nervous system, vessels and possibly the immune system. Compelling experimental and clinical evidence indicates the importance of the vasculature in the pathophysiology of hypertension and as such much emphasis has been placed on the (patho)biology of ROS in the vascular system. A major source for cardiovascular, renal and neural ROS is a family of non-phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox), including the prototypic Nox2 homolog-based NADPH oxidase, as well as other Noxes, such as Nox1 and Nox4. Nox-derived ROS is important in regulating endothelial function and vascular tone. Oxidative stress is implicated in endothelial dysfunction, inflammation, hypertrophy, apoptosis, migration, fibrosis, angiogenesis and rarefaction, important processes involved in vascular remodeling in hypertension. Despite a plethora of data implicating oxidative stress as a causative factor in experimental hypertension, findings in human hypertension are less conclusive. This review highlights the importance of ROS in vascular biology and focuses on the potential role of oxidative stress in human hypertension.

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Section: Vascular Antioxidant Systemsmentioning

confidence: 99%

Section: Vascular Antioxidant Systemsmentioning

confidence: 99%

Reactive oxygen species and vascular biology: implications in human hypertension

2010

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“…Increased ROS production in CKD is compounded by the failure of the endogenous antioxidant defense system [4,15,16]. This is primarily due to the impaired activation of nuclear factor-erythroid-2-related factor 2 (Nrf2), a transcription factor that regulates basal activity and coordinated induction of numerous genes encoding phase-2 detoxifying and antioxidant enzymes and related proteins.…”

Section: Introductionmentioning

confidence: 99%

Dose-dependent deleterious and salutary actions of the Nrf2 inducer dh404 in chronic kidney disease

Vaziri¹,

Liu²,

Farzaneh³

et al. 2015

Free Radical Biology and Medicine

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Oxidative stress and inflammation play a central role in progression and complications of CKD and are, in part, due to impairment of the Nrf2 system which regulates expression of antioxidant and detoxifying molecules. Natural Nrf2 inducing phytochemicals have been shown to ameliorate kidney disease in experimental animals. However due to adverse outcomes clinical trial of synthetic Nrf2 activator, bardoxolone methyl (BARD), in CKD patients was terminated. BARD activates Nrf2 via 2 covalent modification of reactive cysteine residues in Nrf2 repressor molecule, Keap-1. In addition to Nrf2, Keap1 suppresses IKKB, the positive regulator of NF k B. Treatment with BARD analog, dh404, at 5-20 mg/kg/day in diabetic obese Zucker rats exacerbates whereas its use at 2 mg/kg/day in 5/6 nephrectomized rats attenuates CKD progression. We, therefore, hypothesized that deleterious effects of high dose BARD are mediated by activation of NF k B.CKD (5/6 nephrectomized) rats were randomized to receive dh404 (2 or 10mg/kg/day) or vehicle for 12 weeks. Vehicle-treated group exhibited glomerulosclerosis, interstitial fibrosis and inflammation, activation of NF k B, upregulation of oxidative, inflammatory and fibrotic pathways, and suppression of Nrf2 activity and its key target gene products. Treatment with low dose dh404 restored Nrf2 activity and expression of its target genes, attenuated activation of NF k B and fibrotic pathways, and reduced glomerulosclerosis, interstitial fibrosis and inflammation. In contrast treatment with high dh404 dosage intensified proteinuria, renal dysfunction and histological abnormalities, amplified up-regulations of NF k B and fibrotic pathways, and suppression of Nrf2 system. Thus therapy with BARD analogs exerts a dose-dependent dimorphic impact on CKD progression.

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“…Antioxidant enzyme activities are also altered in chronic renal failure (CRF) in which oxidative stress also plays an important part (Modlinger et al, 2004), however, as with diabetic conditions, the true effects are still unclear. Specifically, CAT activity has been found to be down-regulated (Inal et al, 1999;Mimc-Oka et al, 1999;Sindhu et al, 2005) or unaffected (Sommerburg et al, 2002). GSH-Px activity has also been reported to be unaffected in CRF (Sindhu et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…Specifically, CAT activity has been found to be down-regulated (Inal et al, 1999;Mimc-Oka et al, 1999;Sindhu et al, 2005) or unaffected (Sommerburg et al, 2002). GSH-Px activity has also been reported to be unaffected in CRF (Sindhu et al, 2005). These differing results may be due to different responses to oxidative stress depending on cell type, tissue, organ, species or the experimental system used.…”

Section: Introductionmentioning

confidence: 99%

Modulation of Antioxidant Enzyme Expression and Activity by Paraquat in Renal Epithelial NRK-52E Cells

Samai¹,

Boccuti²,

Samai³

et al. 2011

Sierra Leone j. biomed. res.

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Renal toxicity produced by paraquat involves the generation of reactive oxygen species (ROS) which can overwhelm antioxidant defences, leading to oxidant injury. However, there are conflicting reports regarding the activity and/or expression of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) during oxidative stress injury. This study investigated the activity and expression of these enzymes in a renal epithelial cell line following exposure to paraquat. Confluent NRK-52E cells were incubated with increasing concentrations of paraquat (1-100mM) for up to 24 hours. Renal cell death was determined by measurement of lactate dehydrogenase release. Oxidant damage was determined via measurement of malondialdehyde formation and DNA strand breaks. The effects of paraquat on DNA and de novo protein synthesis were determined using radio-labelled thymidine and leucine respectively. ROS generation (superoxide anion and hydroxyl radical formation) was measured using nitrobluetetrazolium and deoxyribose assays. Antioxidant enzyme activities and expression were measured using established biochemical assays and Western blot analysis. Exposure of confluent NRK-52E cells to paraquat resulted in significant cell death involving increased lipid peroxidation, DNA damage and inhibition of DNA and de novo protein synthesis. Renal cell injury and death were secondary to increased ROS generation. Incubation with paraquat reduced SOD and CAT activities; in contrast, GSH-Px activity increased significantly. Although SOD expression was significantly reduced, catalase expression was unaffected. These results indicate that paraquat mediates renal toxicity via oxidative stress involving both an increase in ROS generation and reductions in SOD and CAT activities with a concomitant reduction in SOD expression.

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Expression of catalase and glutathione peroxidase in renal insufficiency

Cited by 68 publications

References 29 publications

Reactive oxygen species and vascular biology: implications in human hypertension

Reactive oxygen species and vascular biology: implications in human hypertension

Dose-dependent deleterious and salutary actions of the Nrf2 inducer dh404 in chronic kidney disease

Modulation of Antioxidant Enzyme Expression and Activity by Paraquat in Renal Epithelial NRK-52E Cells

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