Decreased Glomerular Basement Membrane Heparan Sulfate Proteoglycan in Essential Hypertension

Heintz, Bernhard; Stöcker, Georg; Mrowka, Christian; Rentz, Uwe; Melzer, H; Stickeler, Elmar; Sieberth, H. G.; Greiling, H.; Haubeck, H.-D.

doi:10.1161/01.hyp.25.3.399

Cited by 21 publications

(15 citation statements)

References 19 publications

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“…This agrees with previous estimations of tion signals in skeletal muscle (Fig. 2), because NMJ comprise tional BM HSPG species is not unlikely [49]. The molecular cloning of cDNA encoding human agrin offers new starting only a minute part of the total tissue mass.…”

Section: Discussionsupporting

confidence: 92%

Primary structure and high expression of human agrin in basement membranes of adult lung and kidney

Groffen

Buskens

Kuppevelt

et al. 1998

European Journal of Biochemistry

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Agrin is a heparan sulfate proteoglycan involved in the development of the neuromuscular junction during embryogenesis. In addition to this well-characterized function, agrin may have additional functions in other tissues and during other stages in development. In this study we present the cDNA sequence of human agrin, and demonstrate a high agrin content in adult basement membranes. The N-terminal domain of human agrin is highly similar to that of chick agrin, suggesting a similar function in laminin binding. The presence of three SGXG sequences supports serine-linked glycosylation of the core protein, two sites being particularly favorable for heparan sulfate attachment. Comparison of levels of agrin mRNA in fetal and adult human tissues showed a remarkable upregulation in adult kidney and lung. In both tissues truncated agrin transcripts were detected, lacking the region that encodes the laminin-binding domain. The high transcription levels in lung and kidney corresponded with the accumulation of agrin in the alveolar and glomerular basement membranes, suggesting a filtration-associated function. These data provide new directions for investigating the role of agrin in its different physiological environments, including the basement membranes of the neuromuscular junction, kidney and lung.Keywords : agrin; heparan sulfate proteoglycan ; glomerular basement membrane ; alveolar basement membrane ; neuromuscular junction.Agrin is a heparan sulfate proteoglycan (HSPG) of basement · glycoprotein complex [20]. Thus, agrin may anchor the BM to the cytoskeleton and be involved in signal transduction. Furthermembranes (BM). It induces aggregation of acetylcholine receptors at the neuromuscular junction (NMJ) [1, 2]. The primary more, agrin was identified recently as a major HSPG of the glomerular BM [21]. Here it could participate in the charge-selecstructures of the protein from electric ray, rat, mouse and chick have been reported [3Ϫ6]. The agrin gene was shown to encode tive ultrafiltration process. Agrin could be involved in the storage, activation, inhibition or presentation of various growth multiple isoforms through alternative splicing at three sites, designated x, y and z. These splice variants differ greatly in func-factors, and modulate their effect in a tissue-dependent manner.The human agrin gene was mapped previously to chromotion [6Ϫ9]. During the formation of the NMJ (the contact site of a motoneuron and a skeletal muscle cell), agrin isoforms ex-some 1 [5], but the cDNA structure is unknown. To obtain cDNA clones encoding full-length agrin, we used expressed-sepressed by motoneurons induce the clustering of acetylcholine receptors within the post-synaptic membrane. Isoforms ex-quence-tag information from public databases [18,22]. Here, we report the cDNA sequence of human agrin, and provide data pressed by the muscle cell do not have a clustering activity [6, 10Ϫ12]. Agrin-related proteins are also expressed in non-neural concerning its distribution in human tissues. tissues, suggesting functions in ...

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Section: Discussionsupporting

confidence: 92%

Primary structure and high expression of human agrin in basement membranes of adult lung and kidney

Groffen

Buskens

Kuppevelt

et al. 1998

European Journal of Biochemistry

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“…Due to its high negativity, the HSPG in the GBM is suggested to govern the change-dependent permselectivity of the filtration barrier. Since, as previously shown at physiological pH, the CCG binds primarily to sulfated groups of glycosaminoglycans [22], we may suggest that the reduction in CCG binding to the GBM, in both the normal and hypertensive salt-loaded rats, reflects a loss of sulfated proteoglycans, such as HSPG, as previously found in adriamycin nephropathy [26].…”

Section: Discussionsupporting

confidence: 73%

“…Recently Heintz et al [26] found increased excretion in to the urine o f GBM-specific HSPG in essential hyperten sives as compared to normotensive subjects. These find ings, however, do not provide direct evidence regarding the presumed changes in the distribution of the GBM poly anions.…”

Section: Introductionmentioning

confidence: 99%

Glomerular Basement Membrane Polyanionic Sites and Nitric Oxide in Genetically Salt-Sensitive and Resistant Hypertensive Rats

Hertzan-Levy

Iaina

Wollman

et al. 1997

Kidney Blood Press Res

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Cationic colloid gold, a polycationic histochemical probe, was used to analyze the distribution of glomerular basement membrane (GBM) polyanions, including heparan sulfate protoglycan in genetic salt-sensitive (SBH/Y) and resistant (SBN/Y) hypertensive rats, with or without high dietary salt intake. GBM morphology, renal function and nitric oxide, as measured by plasma and urine nitrite (NO₂) and nitrate (NO₃) were also determined. In the salt-sensitive rats the high-salt dietary intake resulted in severe hypertension, proteinuria and decreased glomerular filtration rate. After 1 month of high-salt intake, the average width of the GBM of salt-sensitive rats was higher by 27% than that of salt-resistant rats. The number of GBM anionic sites (lamina rata externa and interna) was much lower in both salt-sensitive and salt-resistant groups after 1 month of salt loading, 8.04 ± 0.36 and 7.8 ± 0.25 counts/cm, respectively, compared to the respective values of non-salt-loaded animals, 20.58 ± 1.08 counts/cm in the SBH/Y (p < 0.001) and 21 ± 1.86 counts/cm in the SBN/Y (p < 0.001). A decreased nitric oxide production was found in the salt-sensitive rats before and after salt loading compared with the salt-resistant group. No correlation was found between the nitric oxide changes and the GBM modifications. It is concluded that high-salt intake may be deleterious to the permselectivity of the GBM. It is suggested that salt restriction in hypertension may have a beneficial effect in preventing GBM permselectivity changes and proteinuria.

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“…Its activation requires the entry of calcium, angiotensin and adrenergic agonists, which implicated in hypertension, diabetes and heart disease. This suggests the sulfate supplied in GlcNs maybe play a beneficial effect in kidney [37,38].…”

Section: Discussionmentioning

confidence: 97%

Glucosamine Sodium Sulfate Can Penetrate Skin and May Affect Glucose Metabolism in Rats

Zhou¹,

Sui²,

Sun³

et al. 2013

J Drug Metab Toxicol

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Objectives: To investigate whether glucosamine sodium sulfate (GlcNs) can penetrate the skin and the effects of this dietary supplement on glucose metabolism in rats.Methods: GlcNs was radiolabeled with 14 C to test its ability to pass through skin. GlcNs was also orally administered to rats at different doses. Changes in body weight and blood glucose levels were subsequently measured. In addition, levels of key enzymes related to glucose metabolism (SLC2A2 (solute carrier family 2, member 2), SLC2A4 (member 4), HK1 (hexokinase 1), NOS2 (nitric oxide synthase 2), and PRKCA (protein kinase C, alpha) were analyzed in liver and kidney tissues via immunohistochemistry.Results: Radio labeled GlcNs effectively penetrated rat skin. Rats given a daily dose of 250 mg/kg GlcNs exhibited significantly lower levels of blood glucose (p<0.05) than controls. For the 125-mg/kg group, levels of PRKCA and HK1 in kidney were significantly lower (p<0.05) than controls.Conclusions: GlcNs can be administered through the skin. Oral administration of GlcNs does not affect body weight, but may influence glucose metabolism in rats. These findings are important for research concerning diabetes and its complications in patients with arthritis.

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Decreased Glomerular Basement Membrane Heparan Sulfate Proteoglycan in Essential Hypertension

Cited by 21 publications

References 19 publications

Primary structure and high expression of human agrin in basement membranes of adult lung and kidney

Primary structure and high expression of human agrin in basement membranes of adult lung and kidney

Glomerular Basement Membrane Polyanionic Sites and Nitric Oxide in Genetically Salt-Sensitive and Resistant Hypertensive Rats

Glucosamine Sodium Sulfate Can Penetrate Skin and May Affect Glucose Metabolism in Rats

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