Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Label-free protein profiling of formalin-fixed paraffin-embedded (FFPE) heart tissue reveals immediatemitochondrial impairment after ionising radiation
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
Show others and affiliations
2012 (English)In: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, Vol. 75, no 8, 2384-2395 p.Article in journal (Refereed) Published
Abstract [en]

Qualitative proteome profiling of formalin-fixed, paraffin-embedded (FFPE) tissue is advancing the field of clinical proteomics. However, quantitative proteome analysis of FFPE tissue is hampered by the lack of an efficient labelling method. The usage of conventional protein labelling on FFPE tissue has turned out to be inefficient. Classical labelling targets lysine residues that are blocked by the formalin treatment. The aim of this study was to establish a quantitative proteomics analysis of FFPE tissue by combining the label-free approach with optimised protein extraction and separation conditions. As a model system we used FFPE heart tissue of control and exposed C57BL/6 mice after total body irradiation using a gamma ray dose of 3 gray. We identified 32 deregulated proteins (p <= 0.05) in irradiated hearts 24 h after the exposure. The proteomics data were further evaluated and validated by bioinformatics and immunoblotting investigation. In good agreement with our previous results using fresh-frozen tissue, the analysis indicated radiation-induced alterations in three main biological pathways: respiratory chain, lipid metabolism and pyruvate metabolism. The label-free approach enables the quantitative measurement of radiation-induced alterations in FFPE tissue and facilitates retrospective biomarker identification using clinical archives.

Place, publisher, year, edition, pages
2012. Vol. 75, no 8, 2384-2395 p.
Keyword [en]
Label-free, Ionising radiation, Proteomics, Mitochondria, FFPE
National Category
Biochemistry and Molecular Biology
Research subject
Molecular Genetics
Identifiers
URN: urn:nbn:se:su:diva-76467DOI: 10.1016/j.jprot.2012.02.019ISI: 000303974800010OAI: oai:DiVA.org:su-76467DiVA: diva2:526942
Available from: 2012-05-15 Created: 2012-05-15 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Mechanism behind the development of radiation-induced cardiovascular effects
Open this publication in new window or tab >>Mechanism behind the development of radiation-induced cardiovascular effects
2012 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Epidemiological studies on acutely and chronically exposed individuals indicate that ionising radiation could be a risk factor for cardiovascular diseases. Experimental data regarding radiation-induced cardiovascular late effects are limited and biological mechanisms behind these late effects are still unclear. The estimation of risks concerning low-dose rate and low-dose ionising radiation is still challenging due to lack of experimental evidence.

The first paper of the thesis describes the radiation-induced protein alterations in cardiac tissue of total body irradiated mice. We use a label-free proteomic approach to identify altered proteins from formalin-fixed paraffin-embedded heart tissue. Comparison between the cardiac proteomes of control and irradiated mice indicates the respiratory chain, lipid metabolism and pyruvate metabolism pathways are affected. We suggest that these biological processes may play a vital role in radiation-induced cardiovascular diseases.

In the second paper (manuscript) we hypothesized that chronic low-dose rate ionising radiation accelerates premature senescence in endothelial cells and that this may contribute to the radiation-induced cardiovascular diseases. We tested our hypothesis by systematically analysing the growth rate, the number of accumulated senescent cells and the protein expression profiles of the chronically exposed primary human umbilical vein endothelial cells until the cells entered senescence. Decrease in cumulative population doublings and increase in senescent-associated beta-galactosidase stained cells show that chronic exposure to radiation accelerates endothelial cells senescence. Our proteomic results suggest that the cytoskeletal organisation, cell-cell communication and adhesion, inflammation and carbohydrate metabolism were influenced by chronic exposure to radiation. A few deregulated proteins have previously been associated with replicative and stress-induced premature senescence. The results presented here provide new insights on radiation-induced premature senescence in endothelial cells and the changes in protein expression associated with this process.

Place, publisher, year, edition, pages
Stockholm: Department of Genetics, Microbiology and Toxicology, Stockholm University, 2012
National Category
Biochemistry and Molecular Biology
Research subject
Molecular Genetics
Identifiers
urn:nbn:se:su:diva-76473 (URN)
Supervisors
Available from: 2012-09-03 Created: 2012-05-15 Last updated: 2012-10-02Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Yentrapalli, Ramesh
By organisation
Department of Genetics, Microbiology and Toxicology
In the same journal
Journal of Proteomics
Biochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 156 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf