Oxidants in Chronic Kidney Disease

Shah, Sudhir V.; Baliga, Radhakrishna; Rajapurkar, Mohan; Fonseca, Vivian

doi:10.1681/asn.2006050500

Cited by 238 publications

(190 citation statements)

References 119 publications

(106 reference statements)

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“…Circulating mononuclear cells as well as resident renal cells are also targets of angiotensin II and TGF-␤1, both capable of triggering generation of intracellular superoxide and initiating the oxidative stress pathway (38). Increased serum levels of markers of oxidative stress may derive from circulating cells as well as resident renal cells, sharing receptors and activating common pathways of inflammatory response (39).…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress and Galactose-Deficient IgA1 as Markers of Progression in IgA Nephropathy

Camilla

Suzuki

Daprà

et al. 2011

Clinical Journal of the American Society of Nephrology

106

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Summary Background and objectives We assessed the activation of the oxidative stress pathway in patients with IgA nephropathy (IgAN), while evaluating the classic marker of the disease (galactose-deficient serum IgA1). Design, setting, participants, & measurements Sera from 292 patients and 69 healthy controls from Italy and the United States were assayed for advanced oxidation protein products (AOPPs), free sulfhydryl groups on albumin (SH-Alb), and IgA1 with galactose-deficient hinge-region O-glycans (Gd-IgA1). Gd-IgA1 was detected by binding to Helix aspersa agglutinin (HAA) and expressed as total Gd-IgA1 or as degree of galactose deficiency relative to a standard Gd-IgA1 myeloma protein (%HAA). Results Sera from IgAN patients showed higher levels of Gd-IgA1, %HAA, and AOPPs, but lower levels of SH-Alb in comparison to that from healthy controls. Serum levels of AOPPs significantly correlated with serum Gd-IgA1 and %HAA. The relationship between these biomarkers and clinical features at sampling and during follow-up was assessed in 62 patients with long-term follow-up. AOPPs and %HAA correlated with proteinuria at sampling and independently associated with subsequent proteinuria. Levels of AOPPs correlated with rate of decline in renal function after sampling. The combination of a high level of AOPPs and a high level of %HAA associated with decline in estimated GFR. Conclusions Serum levels of aberrantly glycosylated IgA1 are elevated and oxidative stress pathways are activated in patients with IgAN; the intensity of the stress correlated with expression and progression of the disease. We speculate that oxidative stress may modulate the nephrotoxicity of aberrantly glycosylated IgA1 in IgAN.

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Section: Discussionmentioning

confidence: 99%

Oxidative Stress and Galactose-Deficient IgA1 as Markers of Progression in IgA Nephropathy

Camilla

Suzuki

Daprà

et al. 2011

Clinical Journal of the American Society of Nephrology

106

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“…CRT levels are increased during cellular stresses, including oxidative stress and hypoxia (25)(26)(27)(28). Oxidative stress is known to be involved in fibrogenesis in a number of disease processes, including liver, lung, and kidney fibrosis (67)(68)(69)(70)(71). Hypoxia also increases collagen production and deposition in some systems (72).…”

Section: Discussionmentioning

confidence: 99%

Intracellular Calreticulin Regulates Multiple Steps in Fibrillar Collagen Expression, Trafficking, and Processing into the Extracellular Matrix

Graham

Sweetwyne

Pallero

et al. 2010

Journal of Biological Chemistry

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Calreticulin (CRT), a chaperone and Ca2؉ regulator, enhances wound healing, and its expression correlates with fibrosis in animal models, suggesting that CRT regulates production of the extracellular matrix. However, direct regulation of collagen matrix by CRT has not been previously demonstrated. We investigated the role of CRT in the regulation of fibrillar collagen expression, secretion, processing, and deposition in the extracellular matrix by fibroblasts. Mouse embryonic fibroblasts deficient in CRT (CRT ؊/؊ MEFs) have reduced transcript levels of fibrillar collagen I and III and less soluble collagen as compared with wild type MEFs. Correspondingly, fibroblasts engineered to overexpress CRT have increased collagen type I transcript and protein. Collagen expression appears to be regulated by endoplasmic reticulum (ER) calcium levels and intracellular CRT, because thapsigargin treatment reduced collagen expression, whereas addition of exogenous recombinant CRT had no effect. CRT ؊/؊ MEFs exhibited increased ER retention of collagen, and collagen and CRT were co-immunoprecipitated from isolated cell lysates, suggesting that CRT is important for trafficking of collagen through the ER. CRT ؊/؊ MEFs also have reduced type I procollagen processing and deposition into the extracellular matrix. The reduced collagen matrix deposition is partly a consequence of reduced fibronectin matrix formation in the CRT-deficient cells. Together, these data show that CRT complexes with collagen in cells and that CRT plays critical roles at multiple stages of collagen expression and processing. These data identify CRT as an important regulator of collagen and suggest that intracellular CRT signaling plays an important role in tissue remodeling and fibrosis.Calreticulin (CRT), 3 also known as the C1q receptor, is an endoplasmic reticulum (ER) chaperone, and a modulator of intracellular calcium signaling. CRT also is a multifunctional protein that is present in numerous cellular compartments, including the ER, cytoplasm, nucleus, at the cell surface, and as a released protein (1-5). There is evidence to suggest the involvement of CRT in tissue remodeling and wound healing. In a porcine dermal wound healing model, topical application of purified CRT increases the rate of wound healing and wound tensile strength (6). Proteomic data show up-regulation of CRT expression with fibrosis in a rat model of unilateral ureteric obstruction kidney fibrosis and in a mouse model of bleomycininduced lung fibrosis (7). The mechanisms by which CRT regulates tissue remodeling are not well understood, although fibronectin matrix deposition and modulation of cell adhesion, motility, proliferation, and matrix metalloproteinase expression have been implicated (6, 8 -13).CRT has effects on the extracellular matrix (ECM) and cellular responses to the ECM. Fibroblasts overexpressing CRT have increased fibronectin mRNA, protein, and matrix deposition, and cells lacking CRT express less fibronectin than wild type cells (9,14). CRT in the ER is thought to reg...

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“…are experimentally proven to cause further oxidative damage, induce the activity of NF-jb leading inflammatory response. On the other side protein mediated oxidative stress continues the cascade and leads to end stage renal disease [111]. The roles of NTBI and ROS have been depicted in Fig.…”

Section: Iron In Renal Diseasementioning

confidence: 99%

Non Transferrin Bound Iron: Nature, Manifestations and Analytical Approaches for Estimation

Patel

Ramavataram

2012

Ind J Clin Biochem

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Oxidants in Chronic Kidney Disease

Cited by 238 publications

References 119 publications

Oxidative Stress and Galactose-Deficient IgA1 as Markers of Progression in IgA Nephropathy

Oxidative Stress and Galactose-Deficient IgA1 as Markers of Progression in IgA Nephropathy

Intracellular Calreticulin Regulates Multiple Steps in Fibrillar Collagen Expression, Trafficking, and Processing into the Extracellular Matrix

Non Transferrin Bound Iron: Nature, Manifestations and Analytical Approaches for Estimation

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