Degradation of glycated hemoglobin by erythrocytic proteolytic enzymes

Raghothama, Chaerkadi; Rao, Pragna

doi:10.1016/0009-8981(95)06185-1

Cited by 4 publications

(3 citation statements)

References 22 publications

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“…27 These proteins may be responsible for the overall increase of proteases, and/or for a decrease of their inhibitors, found in diabetes, which may be associated with the development and progression of vascular complications independently of glycemic control. [28][29][30][31][32] These data are thus in agreement with the increased HSP71 abundance in the fibroblasts from our type 1 diabetic patients with DN.…”

Section: Discussionsupporting

confidence: 91%

Altered Chaperone and Protein Turnover Regulators Expression in Cultured Skin Fibroblasts from Type 1 Diabetes Mellitus with Nephropathy

et al. 2007

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In type-1 diabetes mellitus (T1DM) with diabetic nephropathy (DN), accumulation of abnormal proteins in the kidney and other tissues may derive from constitutive alterations of intracellular protein recognition, assembly, and turnover. We characterized the proteins involved in these functions in cultured skin fibroblasts from long-term T1DM patients with [DN+] or without [DN-] nephropathy but similar metabolic control, and from matched healthy subjects. 2-D gel electrophoresis and MS-MALDI analysis were employed. The [DN+] T1DM patients, compared with the two other groups, exhibited increased abundance of a high-molecular weight isoform of protein disulphide-isomerase A3 and a decrease of two low-molecular weight isoforms. They also had increased levels of heat shock protein (HSP) 60 kDa isoform #A4, of HSP71 kDa isoform #A30, and of HSP27 kDa isoform #6, whereas the HSP27 kDa isoforms #A90 and #A71 were decreased. Cathepsin beta-2 (#40), the cation-independent mannose 6-phosphate receptor binding protein 1 (CIMPR) (#A27), and annexin 2 (#A9) were also decreased in the [DN+] T1DM patients, whereas the RNA-binding protein regulatory subunity (#38) and the translationally-controlled tumor protein (TCTP) (#A45) were increased. These changes of chaperone-like proteins in fibroblasts may highlight those of the kidney and be patho-physiologically related to the development of nephropathy in T1DM.

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Section: Discussionsupporting

confidence: 91%

Altered Chaperone and Protein Turnover Regulators Expression in Cultured Skin Fibroblasts from Type 1 Diabetes Mellitus with Nephropathy

et al. 2007

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“…Genetic factors also affect the course of complications produced by long-lasting hyperglycaemia: hyperglycaemia-induced oxidative modifications interplay in a complex way with genes [6,7], and a predisposing genetic background could explain the irreversibility of some glucose-induced damage in susceptible patients [8]. Markers for vascular complications, often apparently independent of glycaemic control, are alterations in proteolytic enzyme action [9,10,11,12] and of their inhibitors [9,13,14]. Such changes include unbalanced hyperactivation of plasma-clotting enzymes [15], but also an overall increase in proteolytic activity in various tissues and biological fluids [10,12].…”

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confidence: 99%

“…Markers for vascular complications, often apparently independent of glycaemic control, are alterations in proteolytic enzyme action [9,10,11,12] and of their inhibitors [9,13,14]. Such changes include unbalanced hyperactivation of plasma-clotting enzymes [15], but also an overall increase in proteolytic activity in various tissues and biological fluids [10,12]. Thus a higher-than-norOne of the most troublesome aspects of Type 1 (insulin-dependent) diabetes mellitus are early and severe complications, especially those affecting the vascular bed [1], which are the main causes of increased morbidity and mortality in the diabetic population.…”

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confidence: 99%

Identification and purification from the plasma of Type�1 diabetic subjects of a proteolytically active Grp94

et al. 2003

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Aims/hypothesis. The overall increase in proteolytic activity in diabetes is known to be associated with the development and progression of vascular complications. Our aim was to investigate in detail the molecular nature of this activity in the plasma of Type 1 diabetic subjects. Methods. Plasma of both diabetic and control subjects was subjected to various purification procedures (ion exchange and affinity chromatography, HPLC, immunoprecipitation, electrophoresis, immunoblot and mass analyses) to identify the proteins of interest. Biological activities were measured on specific substrates. Results. In diabetic but not normal plasma we identified the presence of two heat shock proteins, Grp94 (Glucose-regulated protein94) and HSP70. The higher-than-normal proteolytic activity of Grp94 was: (i) directed against casein, but not against endogenous plasma proteins; (ii) fully and specifically inhibited only by anti-Grp94 polyclonal antibodies; and (iii) coupled with low-level ATPase activity. In addition, ATP binding to Grp94 was able to modulate proteolytic activity. We found that Grp94 in plasma circulates only as high molecular mass homo-and hetero-complexes, the latter mostly formed with IgG to which Grp94 is also linked by tenacious binding. Proteolytically-active Grp94 was purified by immunoprecipitation, which co-immunoprecipitated α 1 antitrypsin. Conclusion/interpretation. Our results show the unexpected extracellular location and characteristic biological function of Grp94 even at a late stage of disease. These findings have physiopathological relevance for predicting activation of both autoimmune and inflammatory processes potentially associated with vascular complications. [Diabetologia (2003[Diabetologia ( ) 46:996-1006

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