Quantitative proteomic analysis of fibroblast nuclear proteins after stimulation with mitogen activated protein kinase inhibiting heparan sulfate

Malmström, Johan; Marchese, Jason; Juhász, Péter; Pukac, Laurie; Karnovsky, Manfred L.; Markó-Varga, György; Westergren‐Thorsson, Gunilla

doi:10.1016/j.jchromb.2004.11.054

Cited by 4 publications

(1 citation statement)

References 43 publications

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“…Localization of the HS indicated that the anti‐proliferative effect might be due to direct effects of the HS on nuclear processes, such as gene transcription. Subsequent structural analysis showed that the HS contained a high content of 2‐O‐sulfated iduronic acid and heavily sulfated glucosamine, which led to an inhibition of MAP kinase activation, so leading to an inhibition of cell proliferation through the cell‐cycle pathway (Malmstrom et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Bone‐specific heparan sulfates induce osteoblast growth arrest and downregulation of retinoblastoma protein

Manton¹,

Murali²,

Cool³

et al. 2006

Journal Cellular Physiology

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The heparan sulfate (HSs) sugars of the extracellular matrix (ECM) play a key role during both development and wound repair in regulating the flow of growth and adhesive factors across their cell surface receptors. The aim of this study was to assess the structural and functional differences of HS chains extracted from the conditioned media (soluble), cell surface, and ECM of primary human osteoblast cultures, and to analyze their effects on osteoblast cell growth. HS chains from these compartments were characterized through a combination of enzymatic degradation, anion exchange chromatography, and molecular sieving. Although the chains were all approximately the same size, they varied systematically in their sulfate content, suggesting differences in their protein-binding domains. When added to pre-confluent hFOB1.19 osteoblast cultures, HS doses exceeding 500 ng/ml inhibited proliferation, without affecting viability, irrespective of their origin. Furthermore, HS doses of 500 ng/ml also downregulated retinoblastoma, Cyclin A and CDK1 protein expression, indicating that high doses of osteoblast HS negatively regulate cell cycle, resulting in growth arrest; when high doses of HS were withdrawn after a prolonged period, linear cell growth was reestablished. Thus, despite differences in sulfation, HS from either the soluble, cell surface, or matrix compartments of primary human osteoblast cultures are functionally similar with respect to their effects on growth. Binding assays revealed that the HS chains bound TGFbeta1, a known inhibitor of osteoprogenitor growth, at higher affinity than a suite of other bone-related, heparin-binding growth factors. Overcoming such sugar-mediated inhibition may prove important for wound repair.

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Section: Discussionmentioning

confidence: 99%

Bone‐specific heparan sulfates induce osteoblast growth arrest and downregulation of retinoblastoma protein

Manton¹,

Murali²,

Cool³

et al. 2006

Journal Cellular Physiology

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Proteomics: A new research area for the biomedical field

Malmström

Markó-Varga

2005

Journal of Organ Dysfunction

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Recent advancements in differential proteomics based on stable isotope coding

Julka

2005

Briefings in Functional Genomics and Proteomics

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Stable isotope coding continues to be a powerful approach in comparative proteomics. This review focuses on recent developments in stable isotope coding-based strategies targeted towards protein expression, protein interactions with other biomolecules, post-translational modifications and absolute quantification. The focus of the bulk of proteomics studies is still on protein expression. An important recent application of isotope coding has been in organelle proteomics. The review ends with the conclusion that isotope coding remains an integral part of quantitative proteomics. There is, however, a need to develop coding strategies which can differentiate changes in protein expression and post-translational modification, address issues of protein dynamic range and facilitate real-time detection of proteins which show a statistically significant change after stimulus.

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Quantitative proteomic analysis of fibroblast nuclear proteins after stimulation with mitogen activated protein kinase inhibiting heparan sulfate

Cited by 4 publications

References 43 publications

Bone‐specific heparan sulfates induce osteoblast growth arrest and downregulation of retinoblastoma protein

Bone‐specific heparan sulfates induce osteoblast growth arrest and downregulation of retinoblastoma protein

Proteomics: A new research area for the biomedical field

Recent advancements in differential proteomics based on stable isotope coding

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