Apolipoprotein CII and lipoprotein lipase in human nephrotic syndrome

Kashyap, Moti L.; Srivastava, Laxmi S.; Hynd, Barbara A.; Brady, D; Perisutti, Gladys; Glueck, Charles J.; Gartside, Peter S.

doi:10.1016/0021-9150(80)90025-8

Cited by 60 publications

(22 citation statements)

References 37 publications

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“…Overexpression of human apoCIII in transgenic mice results in hypertriglyceridemia (13). ApoCIII is a 79-residue, 8.8-kDa polypeptide (14) with three known isoforms that differ in terms of glycosylation, CIII 0 (no sialic acid), CIII 1 (one sialic acid residue), and CIII 2 (two sialic acid residues), contributing Ϸ10%, 55%, and 35%, respectively, of total plasma apoCIII (15). Mutagenesis of the glycosylation site and expression in stable cell lines suggest that intracellular glycosylation is not required for the transport and secretion functions (16).…”

Section: Resultsmentioning

confidence: 99%

Apolipoprotein CIII promotes Ca ²⁺ -dependent β cell death in type 1 diabetes

Juntti‐Berggren

Refai

Appelskog

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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In type 1 diabetes (T1D), there is a specific destruction of the insulin secreting pancreatic ␤ cell. Although the exact molecular mechanisms underlying ␤ cell destruction are not known, sera from T1D patients have been shown to promote Ca 2؉ -induced apoptosis. We now demonstrate that apolipoprotein CIII (apoCIII) is increased in serum from T1D patients and that this serum factor both induces increased cytoplasmic free intracellular Ca 2؉ R esearch over the last 30 years has established that type 1 diabetes (T1D) is an autoimmune disease, but the mechanisms͞events that trigger the initiation and progression of the disease are still not identified. Genetic, immunological, and environmental factors are involved in the pathogenesis of T1D and most likely the events involved differ between different patients. Voltage-gated L-type Ca 2ϩ channels have an important physiological role in pancreatic ␤ cell signal transduction (1). These channels constitute an essential link between transient changes in membrane potential and insulin release. Changes in cytoplasmic free intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) in the ␤ cell are associated with the activation of a spectrum of intracellular signals and are strictly regulated because prolonged high [Ca 2ϩ ] i is harmful to the cells. Sera from newly diagnosed T1D patients have been shown to increase the activity of voltage-gated L-type Ca 2ϩ channels in ␤ cells, resulting in increased [Ca 2ϩ ] i upon depolarization and ␤ cell apoptosis, effects that can be prevented by Ca 2ϩ channel blockers (2). The key question has been what factor in T1D serum that is responsible for the changes in [Ca 2ϩ ] i . In the present study, we have revealed the identity of a key factor in T1D sera that increases [Ca 2ϩ ] i as well as promotes apoptosis and found it to correspond to apolipoprotein CIII (apoCIII). The fact that not all sera from T1D patients affected [Ca 2ϩ ] i indicates that T1D is not caused by a single factor like apoCIII, which is in agreement with clinical observations, suggesting that different factors can act in concert with the autoimmune abnormalities resulting in ␤ cell destruction. MethodsMedia. The basal medium used both for isolation of cells and for experiments was a Hepes buffer (pH 7.4), containing: 125 mM NaCl, 5.9 mM KCl, 1.3 mM CaCl 2 , 1.2 mM MgCl 2 , and 25 mM Hepes. BSA was added to the medium at a concentration of 1 mg͞ml. For cell culture, RPMI medium 1640 was supplemented with 100 g͞ml streptomycin, 100 units of penicillin, and 10% FCS, normal human, or diabetic serum.Preparation of Cells. Adult mice from a local colony (3) were starved overnight. Pancreatic islets were isolated by a collagenase technique, and cell suspensions were prepared as described (4, 5). Cells were seeded onto glass coverslips and cultured at 37°C in a humidified atmosphere of 5% CO 2 in air.Preparation and Purification of Sera. Sera from T1D patients and control subjects were collected, identically sterile-processed, and stored frozen at Ϫ20°C until used. The sera we...

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Section: Resultsmentioning

confidence: 99%

Apolipoprotein CIII promotes Ca ²⁺ -dependent β cell death in type 1 diabetes

Juntti‐Berggren

Refai

Appelskog

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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“…Since the C-apolipoproteins constitute the major prot ein part of VLDL, one would expect a close correlation between the level of the triglycerides, which essentially are transported within this lipoprotein class, and the concentration of the C-apolipoproteins. Indeed, such a correlation was observed for apolipoprotein C-III (22,24,25). Surprisingly, a significant correlation was found between apolipoproteifi CJ and total cholesterol in both sexes, while the correlation between apolipoprotein C-I and triglycerides reached the level of significance only in normal men.…”

Section: Discussionmentioning

confidence: 91%

“…According to Kashyap et al, apolipoprotein C-III makes up 18% of apo VLDL (24). This would leave about 12% for apolipoprotein C-II if one assumes that the Capolipoproteins contribute about 45% of the VLDLproteins.…”

Section: Discussionmentioning

confidence: 99%

Enzyme-Linked Immunosorbent Assay for Apolipoprotein C-I

Riesen¹,

Sturzenegger²

1986

Clinical Chemistry and Laboratory Medicine

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Summary:A non-competitive Sandwich enzyme-linked immunosorbent assay for apolipoprotein C-I was developed. Sheep antibody to this apolipoprotein C-I, purifled by affmity chromatography, was used for coating the wells of a microtiter plate and äs a conjugate with alkaline phosphatase. The linear ränge of the assay was from 80 ng to 15ng. It was sensitive down to 5ng. The intra-assay Variation coefficient was 2.8%, and the inter-assay Variation coefficient 5.3%. The mean concentration of apolipoprotein C-I was 61 ± 20 mg/1 in healthy normal males, and 65 + 19 mg/1 in females. Apolipoprotein C-I levels were positively correlated with the total cholesterol concentration in both sexes (p < 0.002). A significant correlation with triacylglycerol was only observed in males (p < 0.05). A significant increase of apolipoprotein C-I was observed in type V hyperlipoproteinaemia, and in the only studied case of type III. Enzymimmunoassay (ELISA) zur quantitativen Bestimmung von Apolipoprotein C-I

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“…Several studies have revealed that peripheral catabolism of triglyceride-laden lipoproteins (i.e., CM and VLDL) is impaired and postheparin LPL activity and mass are reduced in clinical nephrosis [15,38,39]. In animal models of kidney disease, significant reduction of LPL activity, mRNA level or protein mass is observed in the cardiac muscle, skeletal muscle and adipose tissues [16-18,33,40,41].…”

Section: Discussionmentioning

confidence: 99%

Preventive effect of Ibrolipim on suppressing lipid accumulation and increasing lipoprotein lipase in the kidneys of diet-induced diabetic minipigs

Liu

Wang

et al. 2011

Lipids Health Dis

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BackgroundThe role of renal lipoprotein lipase (LPL) per se in kidney diseases is still controversial and obscure. The purpose of this study was to observe the preventive effects of Ibrolipim, a LPL activator, on lipid accumulation and LPL expression in the kidneys of minipigs fed a high-sucrose and high-fat diet (HSFD).MethodsMale Chinese Bama minipigs were fed a control diet or HSFD with or without 0.1 g/kg/day Ibrolipim for 5 months. Body weight, plasma glucose, insulin, lipids, LPL activity, and urinary microalbumin were measured. Renal tissue was obtained for detecting LPL activity and contents of triglyceride and cholesterol, observing the renal lipid accumulation by Oil Red O staining, and examining the mRNA and protein expression of LPL by real time PCR, Western Blot and immunohistochemistry.ResultsFeeding HSFD to minipigs caused weight gain, hyperglycemia, hyperinsulinemia, hyperlipidemia and microalbuminuria. HSFD increased plasma LPL activity while it decreased the mRNA and protein expression and activity of LPL in the kidney. The increases in renal triglyceride and cholesterol contents were associated with the decrease in renal LPL activity of HSFD-fed minipigs. In contrast, supplementing Ibrolipim into HSFD lowered body weight, plasma glucose, insulin, triglyceride and urinary albumin concentrations while it increased plasma total cholesterol and HDL-C. Ibrolipim suppressed the renal accumulation of triglyceride and cholesterol, and stimulated the diet-induced down-regulation of LPL expression and activity in the kidney.ConclusionsIbrolipim exerts renoprotective and hypolipidemic effects via the increase in renal LPL activity and expression, and thus the increased expression and activity of renal LPL play a vital role in suppressing renal lipid accumulation and ameliorating proteinuria in diet-induced diabetic minipigs.

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Apolipoprotein CII and lipoprotein lipase in human nephrotic syndrome

Cited by 60 publications

References 37 publications

Apolipoprotein CIII promotes Ca ²⁺ -dependent β cell death in type 1 diabetes

Apolipoprotein CIII promotes Ca ²⁺ -dependent β cell death in type 1 diabetes

Enzyme-Linked Immunosorbent Assay for Apolipoprotein C-I

Preventive effect of Ibrolipim on suppressing lipid accumulation and increasing lipoprotein lipase in the kidneys of diet-induced diabetic minipigs

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Apolipoprotein CII and lipoprotein lipase in human nephrotic syndrome

Cited by 60 publications

References 37 publications

Apolipoprotein CIII promotes Ca 2+ -dependent β cell death in type 1 diabetes

Apolipoprotein CIII promotes Ca 2+ -dependent β cell death in type 1 diabetes

Enzyme-Linked Immunosorbent Assay for Apolipoprotein C-I

Preventive effect of Ibrolipim on suppressing lipid accumulation and increasing lipoprotein lipase in the kidneys of diet-induced diabetic minipigs

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Apolipoprotein CIII promotes Ca ²⁺ -dependent β cell death in type 1 diabetes

Apolipoprotein CIII promotes Ca ²⁺ -dependent β cell death in type 1 diabetes