Receptor for advanced glycation endproduct (RAGE)–mediated nuclear factor‐κB activation in vasculitic neuropathy

Haslbeck, Karl-Matthias; Bierhaus, Angelika; Erwin, Schliecher; Kirchner, A.; Nawroth, Peter P.; Schlötzer, Ursula; Neundörfer, B.; Heuss, Dieter

doi:10.1002/mus.20039

Cited by 55 publications

(37 citation statements)

References 54 publications

(65 reference statements)

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“…The binding of AGEs to their receptor (RAGE) can activate the proinflammatory transcription factor NF-B p65, which allows its translocation to the nucleus, where it regulates the expression of a large number of cytokine genes, including tumor necrosis factor-␣ (TNF-␣), interleukin-1␤ (IL-1␤) and RAGE itself. The process seems to be responsible for maintaining acute and chronic inflammation in various cell types (31,(33)(34)(35). A series of studies of sural nerve biopsies by Haslbeck et al suggest that the RAGE pathway plays a critical proinflammatory role in vasculitic neuropathy and may be one of the first steps in the pathogenesis of IGT-related polyneuropathy (PNP) even before chronic hyperglycemia occurs (9,33,34).…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Grape Seed Proanthocyanidin Extracts on Cerebral Cortex of Streptozotocin-Induced Diabetic Rats through Modulating AGEs/RAGE/NF-κB Pathway

Lü

et al. 2010

J Nutr Sci Vitaminol

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Summary Diabetic encephalopathy is a severe complication in patients with long-term hyperglycemia. Oxidative stress is thought to be closely implicated in this disorder, so in this study, we examined whether grape seed proanthocyanidin extract (GSPE), a naturally occurring antioxidant derived from grape seeds, could reduce the injuries in the cerebral cortex of diabetic rats by modulating advanced glycation end products (AGEs)/the receptor for AGEs (RAGE)/nuclear factor-kappa B p65 (NF-B p65) pathway, which is crucial in oxidative stress. Body weight and serum AGEs were tested; cerebral cortexes were isolated for morphological observations and the pyramidal cell layers were immunohistochemically stained for the detection of RAGE, NF-B p65, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) as well. For RAGE and NF-B p65, quantitative reverse transcriptase coupled to polymerase chain reaction (RT-PCR) was employed for determination of mRNA levels, and western blot was used to detect protein expression. Our results showed that long term hyperglycemia in diabetic rats caused the degeneration of neurons and the up-regulation of serum AGEs, and also the up-regulation of RAGE, NF-B p65, VCAM-1 and ICAM-1 in the brain. We found that GSPE treatment improved the pathological changes of diabetic rats by modulating the AGEs/RAGE/NF-B p65 pathway. This study enables us to further understand the key role that the AGEs/RAGE/NF-B pathway plays in the pathogenesis of diabetic encephalopathy, and confirms that GSPE might be a therapeutical means to the prevention and treatment of this disorder.

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Section: Discussionmentioning

confidence: 99%

Protective Effects of Grape Seed Proanthocyanidin Extracts on Cerebral Cortex of Streptozotocin-Induced Diabetic Rats through Modulating AGEs/RAGE/NF-κB Pathway

Lü

et al. 2010

J Nutr Sci Vitaminol

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“…CD68 is also a member of the scavenger receptor family and typically functions to clear cellular debris, promote phagocytosis, and mediate the recruitment and activation of macrophages. Based on immunohistochemistry, CD68 is histiocytic (similar to the T-lymphocytic marker CD3) and is associated with multicentric reticulohistiocytosis [41] , rheumatoid arthritis [42] , Crohn's disease [43] , and vasculitic neuropathies [44] . Besides the genes mentioned above, the gene expression of other NF-κB downregulated genes, including SAA2, LTB, TNFRSF9, was confirmed by real-time qRT-PCR.…”

Section: Discussionmentioning

confidence: 99%

Microarray analysis reveals the inhibition of nuclear factor-kappa B signaling by aristolochic acid in normal human kidney (HK-2) cells

Chen

Chiang

et al. 2010

Acta Pharmacol Sin

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Aim: To study the molecular mechanism underlying the effect of aristolochic acid (AA), a major active component of plants from the Aristolochiaceae family using microarray analysis. Methods: Human kidney (HK-2) cells were treated with AA (0, 10, 30, and 90 μmol/L) for 24 h, and the cell viability was measured by a 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay. Complementary DNA microarrays were used to investigate the gene expression pattern of HK-2 cells exposed to AA in triplicate. A quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assay was used to verify the microarray data for selected nuclear factor kappa B (NF-κB)-regulated genes. Furthermore, the subcellular localization of NF-κB p65 was visualized by immunofluorescence confocal microscopy in HK-2 cells. The NF-κB activity was examined by a luciferase reporter assay in HK-2/NF-κB transgenic cells. Results: AA exhibited a dose-dependent cytotoxic effect in HK-2 cells and induced alterations in the gene expression profiles related to the DNA damage response, DNA repair, macromolecule metabolic process, carbohydrate metabolic process, DNA metabolic process, apoptosis, cell cycle, and transcription. In addition, 9 biological pathways associated with immunomodulatory functions were downregulated in AA-treated HK-2 cells. A network analysis revealed that NF-κB played a central role in the network topology. Among NF-κB-regulated genes, 8 differentially expressed genes were verified by qRT-PCR. The inhibition of NF-κB activity by AA was further confirmed by immunofluorescence confocal microscopy and by NF-κB luciferase reporter assay. Conclusion: Our data revealed that AA could suppress NF-κB activity in normal human cells, perhaps partially accounting for the reported anti-inflammatory effects of some plants from the genus Aristolochia.Keywords: aristolochic acid; microarray analysis; nuclear factor-kappa B; human kidney HK-2 cells; confocal microscopy; luciferase reporter assay Acta Pharmacologica Sinica (2010) 31: 227-236; doi: 10.1038/aps.2009 Original Article # These authors contributed equally to this work. * To whom correspondence should be addressed. [7,8] . AA was found to possess anti-inflammation effects as demonstrated by its ability to inhibit phospholipase A 2 (PLA 2 ) when administered by intramuscular or intraperitoneal injection [9,10] . Furthermore, AA was also reported to inhibit Group I PLA 2 in humans with sepsis [11] . From in vitro studies, AA has been shown to suppress phospholipohydration of PLA 2 derived from human synovial fluid, cobra venom, porcine pancreas, and human platelets [12] . The anti-inflammatory activities of AA in different models of inflammation have promoted its use in many countries in herbal formulations for arthritis, rheumatism, gout and chronic inflammatory skin diseases [13,14] . Moreover, double-blind studies in healthy volunteers show that AA increased the phagocytic activity of peripheral granulocytes after treatment with AA 0.9 mg/d for three to ten consecutive days [...

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“…This large heterogeneous group of uremic toxins has been shown to induce tissue dysfunction, in part through interaction with AGE-specific receptors on monocytes and other cells [19] consistently inducing proinflammatory gene expression via necrosis factor-κB [20]. The time course of serum concentrations of AGEs in the current study reveals that generation of AGEs during the interdialytic time period is high.…”

Section: Discussionmentioning

confidence: 79%

Treatment Frequency and Efficiency in Hemodiafiltration

et al. 2013

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Background: One of the main objectives of dialysis is uremic retention product elimination. Efficiency of dialysis modalities varies both regarding the range of solutes removed and the extent of such removal. We analyzed plasma (or blood) concentrations of marker solutes in intermittent treatment schedules using hemodiafiltration (HDF). Methods: Elimination and rebound of uremic solutes were measured in 10 patients (77 ± 12 kg, 66.5 ± 9.2 years) treated with postdilution HDF in one 4-hour treatment and in two 2-hour treatments on consecutive days (Polyflux 2.1 m², QB 451 ± 53 ml/min, QD 598 ± 13 ml/min). Blood urea, creatinine, phosphate, β₂-microglobulin, complement factor D and advanced glycation end products were analyzed before, during and after HDF for 24-48 h. Results: Applying two 2-hour HDF treatments on consecutive days resulted in significantly lower plasma (or blood) levels of urea, creatinine, phosphate, β₂-microglobulin, and advanced glycation end products after 48 h than using one 4-hour session. Conclusions: Increased treatment frequency could further optimize blood purification in HDF therapy.

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Receptor for advanced glycation endproduct (RAGE)–mediated nuclear factor‐κB activation in vasculitic neuropathy

Cited by 55 publications

References 54 publications

Protective Effects of Grape Seed Proanthocyanidin Extracts on Cerebral Cortex of Streptozotocin-Induced Diabetic Rats through Modulating AGEs/RAGE/NF-κB Pathway

Protective Effects of Grape Seed Proanthocyanidin Extracts on Cerebral Cortex of Streptozotocin-Induced Diabetic Rats through Modulating AGEs/RAGE/NF-κB Pathway

Microarray analysis reveals the inhibition of nuclear factor-kappa B signaling by aristolochic acid in normal human kidney (HK-2) cells

Treatment Frequency and Efficiency in Hemodiafiltration

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