| 2. |
- Millioni, R., et al.
(författare)
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Abnormal cytoskeletal protein expression in cultured skin fibroblasts form type 1 diabetes mellitus patiens with nephropathy: A proteomic approach
- 2008
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Ingår i: Proteomics Clinical Applications. - : Wiley. - 1862-8354 .- 1862-8346. ; 2:4, s. 492-503
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Tidskriftsartikel (refereegranskat)abstract
- Diabetic nephropathy (DN) develops in about 40% of insulin-dependent type 1 diabetes mellitus (TlDM) patients, and is associated not only with diabetes duration and metabolic control, but also with a genetic predisposition. Constitutive alterations of cytoskeletal proteins may play a role in the development of DN. We investigated the expression of these proteins in cultured skin fibroblasts, obtained from long-term TlDM patients with and without DN but comparable metabolic control, and from matched healthy subjects, by means of 2-DE electrophoresis and MS-MALDI analyses. In T1DM with DN, compared to the other two groups, quantitative analyses revealed an altered expression of 17 spots (p < 0.05-p < 0.01), corresponding to 12 unique proteins. In T1DM with DN, beta-actin and three isoforms of tubulin beta-2 chain, tropomodulin-3, and LASP-1 were decreased, whereas two tubulin beta-4 chain isoforms, one alpha actinin4 isoform, membrane-organizing extension spike protein (MOESIN), FLJ00279 (corresponding to a fragment of myosin heavy chain, non-muscle type A), vinculin, a tropomyosin isoform, and the macrophage capping protein were increased. A shift in caldesmon isoforms was also detected. These results demonstrate an association between DN and the constitutive expression of cytoskeleton proteins in cultured skin fibroblasts from TlDM with DN, which may retain pathophysiologycal implications.
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| 3. |
- Tessari, P, et al.
(författare)
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Altered chaperone and protein turnover regulators expression in cultured skin fibroblasts from type 1 diabetes mellitus with nephropathy
- 2007
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 6:3, s. 976-986
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Tidskriftsartikel (refereegranskat)abstract
- 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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