Glycosaminoglycan synthesis by glomeruli in vivo and in vitro

Dm, Brown; Af, Michael; Tr, Oegema

doi:10.1016/0304-4165(81)90351-2

Cited by 44 publications

(25 citation statements)

References 4 publications

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“…Metabolic turnover studies in rat glomeruli in vivo and in vitro using 35 SO 4 have shown differential turnover of both 35 S-heparan sulfate and 35 S-chondroitin and -dermatan sulfates by isolated rat glomerular components, which are dependent on the incubation conditions. 105 Although there is now a general agreement on the chemical composition of GBM, 106 -107 the exact nature of the constituent polypeptide chains is still unknown. 108 The chemistry of other glomerular components is less well understood.…”

Section: Biochemistry Of Diabetic Basement Membranesmentioning

confidence: 99%

Kidney Complications

Brown¹,

Andres²,

Hostetter³

et al. 1982

Diabetes

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Diabetic glomeruiosclerosis in man and in all spontaneous-onset and chemically induced diabetes in experimental models is characterised by diffuse increase in mesangial matrix and glomerular basement membrane thickening. The most prominent features of the biochemical changes in the glomerular basement membrane are increase in the collagen-Bike components, decreased sialic acid, and increased glucosylation. However, the heterogeneity of the various glycoprotein components of the glomerular basement membrane and related components of the mesangium make comparative biochemistry difficult. Increased glomerular blood flow with no apparent alterations in the glomerular filtration coefficient in diabetes may be attributed to altered vascular control mechanisms which may include both hormonal mediation as well as changes in end-organ responsiveness. Although proteinuria is a common manifestation of diabetic involvement of the glomerulus, there is little biochemical or physiologic evidence as to the specific causes of increased glomerular filtration apparatus permeability. Further information as to the pathogenesis of diabetic vascular disease of the kidney and the ability to reverse pathologic changes by correction of the metabolic milieu will require analysis of carefully selected animal models. Particular care in experimental design must include the ability to integrate pathology, physiology, and biochemistry in each model in order to relate the information to human renal diabetic complications. DIABETES 31 (Suppl. 1):71-81, 1982. I nvestigators working with animal models of diabetes are frequently asked, "Can the results be extrapolated to man?" Perhaps the question is best answered by establishing general criteria for the value of animal model systems and examining how well any specific model fulfills them. This paper will review animal models of diabetes with Address reprint requests to

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Section: Biochemistry Of Diabetic Basement Membranesmentioning

confidence: 99%

Kidney Complications

Brown¹,

Andres²,

Hostetter³

et al. 1982

Diabetes

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“…Heparan sulfate is the predominant GAG species in basement membranes, although small amounts of chondroitin sulfate and dermatan sulfate have been found (1)(2)(3)(4)(5)(6). This compound is a polyanion with a net negative charge and is believed to influence electrochemical properties and to contribute to the charge-selective nature of the glomerular capillary barrier (7)(8)(9).…”

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confidence: 98%

Undersulfation of Glomerular Basement Membrane Heparan Sulfate in Experimental Diabetes and Lack of Correction With Aldose Reductase Inhibition

Cohen

Klepser²,

Wu³

1988

Diabetes

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In this study we examined the effect of experimental diabetes and of treatment with an aldose reductase inhibitor on the level of sulfation of glomerular basement membrane (GBM) heparan sulfate, the principal glycosaminoglycan in this extracellular matrix. Glycosaminoglycans were isolated from GBM purified from control, streptozocin-induced diabetic, and sorbinil-treated diabetic rats and analyzed for sulfate and uronate content. Glomerular yields from diabetic kidneys were greater than those from control animals, but the amount of sulfate per glomerulus in diabetic samples, both untreated and sorbinil treated, did not differ significantly from that in control samples. However, the sulfate-to-uronate ratio in heparan sulfate isolated from diabetic GBM (0.34 +/- 0.08) was significantly less than in control samples (0.69 +/- 0.11), and treatment of diabetic rats with an aldose reductase inhibitor did not correct this reduced ratio (0.36 +/- 0.06). The results indicate that there is an undersulfation of heparan sulfate of GBM in experimental diabetes, an abnormality that may contribute to loss of anionic sites and decreased charge selectivity of the glomerular filtration barrier. The findings further suggest that this abnormality results from disturbances in glycosaminoglycan synthesis and/or metabolism in diabetes that are independent of polyol-pathway activation in the renal glomerulus.

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“…These probes failed to bind to GBM after in situ digestion with enzymes specific for the glycosaminoglycan heparan sulfate [60]. Biochemical characterizations of glomeruli radiolabeled in vivo [11,79] or in vitro [11,64] with [35S]sulfate have revealed the presence within a 4 to 24-h incubation of newly synthesized glycosaminoglycans in isolated GBM and mesangium. These include heparan sul-fate (HS), chondroitin sulfate (CS) and dermatan sulfate (DS), with HS representing the majority (65 %-85 %) of these constituents.…”

Section: Glycosaminoglycans and Proteoglycansmentioning

confidence: 97%