Renal clearance of glycolaldehyde- and methylglyoxal-modified proteins in mice is mediated by mesangial cells through a class A scavenger receptor (SR-A)

Nakajou, Keisuke; Horiuchi, Seikoh; Sakai, Masakazu; Haraguchi, Nozomu; Tanaka, M.; Takeya, Motohiro; Otagiri, Masaki

doi:10.1007/s00125-004-1646-6

Cited by 16 publications

(10 citation statements)

References 38 publications

(47 reference statements)

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“…Protein labeling with 125 I. AOPPs-HSA and HSA were labeled with 125 I by Iodo-Gen (Pierce), as previously described (35). A solution containing 10 l of Na 125 I solution and 0.5 mg of proteins in 0.2 ml of 0.1 M sodium phosphate buffer (pH 7.4) in an Iodo-Genadhered test tube was incubated for 30 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

CD36 is one of important receptors promoting renal tubular injury by advanced oxidation protein products

Iwao¹,

Nakajou²,

Nagai³

et al. 2008

American Journal of Physiology-Renal Physiology

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Chronic accumulation of plasma advanced oxidation protein products (AOPPs) promotes renal fibrosis. However, the mechanism at the cellular level has not been clarified. In the present study, endocytic assay of human proximal tubular cells (HK-2 cells) demonstrated that AOPPs-human serum albumin (HSA) (in vitro preparations of chloramine- modified HSA) were significantly endocytosed in a dose-dependent manner at a higher level than HSA. The expression of CD36, a transmembrane protein of the class B scavenger receptor, in HK-2 cells was confirmed in the immunoblot analysis. In a cellular assay using overexpressing human CD36 in Chinese hamster ovary (CHO) cells, AOPPs-HSA were significantly endocytosed by CD36-CHO cells but not by mock-CHO cells. Furthermore, the endocytic association and degradation of AOPPs-HSA by HK-2 cells was significantly inhibited by anti-CD36 antibody treatment, suggesting that CD36 is partly involved in the uptake of AOPPs-HSA by HK-2 cells. AOPPs-HSA upregulated the expression of CD36 in a dose-dependent manner. In addition, AOPPs-HSA upregulated the generation of intracellular reactive oxygen species and the secretion of transforming growth factor (TGF)-beta1 in HK-2 cells, whereas anti-CD36 antibody neutralizes the upregulation of TGF-beta1. These results suggest that AOPPs-HSA may cause renal tubular injury via the CD36 pathway.

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Section: Methodsmentioning

confidence: 99%

CD36 is one of important receptors promoting renal tubular injury by advanced oxidation protein products

Iwao¹,

Nakajou²,

Nagai³

et al. 2008

American Journal of Physiology-Renal Physiology

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“…Recently, the DJ‐1 family member Hsp31 was observed to degrade MG‐modified proteins having a deglycase‐like function . Kidney eliminates a major part of circulating AGE and dicarbonyl adducts, as after filtration they are reabsorbed by the tubular and mesangial cells, degraded in the lysosomes and eliminated as AGE‐amino acids …”

Section: The Promise Of New Therapeutic Targetsmentioning

confidence: 99%

Methylglyoxal in Metabolic Disorders: Facts, Myths, and Promises

Matafome

Rodrigues

Sena

et al. 2016

Medicinal Research Reviews

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Glucose and fructose metabolism originates the highly reactive byproduct methylglyoxal (MG), which is a strong precursor of advanced glycation end products (AGE). The MG has been implicated in classical diabetic complications such as retinopathy, nephropathy, and neuropathy, but has also been recently associated with cardiovascular diseases and central nervous system disorders such as cerebrovascular diseases and dementia. Recent studies even suggested its involvement in insulin resistance and beta-cell dysfunction, contributing to the early development of type 2 diabetes and creating a vicious circle between glycation and hyperglycemia. Despite several drugs and natural compounds have been identified in the last years in order to scavenge MG and inhibit AGE formation, we are still far from having an effective strategy to prevent MG-induced mechanisms. This review summarizes the endogenous and exogenous sources of MG, also addressing the current controversy about the importance of exogenous MG sources. The mechanisms by which MG changes cell behavior and its involvement in type 2 diabetes development and complications and the pathophysiological implication are also summarized. Particular emphasis will be given to pathophysiological relevance of studies using higher MG doses, which may have produced biased results. Finally, we also overview the current knowledge about detoxification strategies, including modulation of endogenous enzymatic systems and exogenous compounds able to inhibit MG effects on biological systems.

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“…56) Interestingly, we recently found that advanced glycation end product albumins, produced by reacting albumin with glucose or reducing sugar are cleared from the kidney by scavenger receptor A-mediated endocytic uptake by mesangial cells. 57) Extracorporeal Clearance using HSA Albumin can be used to clear the body of certain endogenous toxins. Among these are bilirubin, bile acids, and uremic toxins.…”

Section: Drug-albumin Binding In Disease Statesmentioning

confidence: 99%

A Molecular Functional Study on the Interactions of Drugs with Plasma Proteins

Otagiri

2005

Drug Metabolism and Pharmacokinetics

200

137

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The binding of drugs to plasma proteins, such as albumin and alpha1-acid glycoprotein (AGP) is a major determinant in the disposition of drugs. A topology analysis of drug binding sites on HSA and AGP was determined using various methods, including spectroscopy, QSAR, photoaffinity labeling and site directed mutagenesis. Recombinant albumin was found to be useful for rapidly identifying drug binding sites. The binding sites on AGP are not completely separated but are partially overlapped, and Trp, Tyr, Lys and His residues in the drug binding pockets play important roles in this process. Drug displacement is somewhat complex, due to the involvement of multiple effects. The reduced binding in uremic patients may be explained by a mechanism that involves a combination of direct displacement by free fatty acids as well as cascade effects of free fatty acids and unbound uremic toxins for significant inhibition in serum binding. Albumin-containing dialysate is useful for the extracorporeal removal of endogenous toxins and in the treatment of drug overdoses. Oxidized albumin is a useful biomarker for the quantitative and qualitative evaluation of oxidative stress. Interestingly, AGP undergoes a structural transition to a unique structure that differs from the native and denatured states, when it interacts with membranes.

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Renal clearance of glycolaldehyde- and methylglyoxal-modified proteins in mice is mediated by mesangial cells through a class A scavenger receptor (SR-A)

Cited by 16 publications

References 38 publications

CD36 is one of important receptors promoting renal tubular injury by advanced oxidation protein products

CD36 is one of important receptors promoting renal tubular injury by advanced oxidation protein products

Methylglyoxal in Metabolic Disorders: Facts, Myths, and Promises

A Molecular Functional Study on the Interactions of Drugs with Plasma Proteins

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