Research for the Environment

Effect of Volatile Organic Compounds on the protein expression of Human immune cells

Exposure to Volatile Organic Compounds (VOCs) is a major occupational and environmental health concern. Inhalation of VOCs can cause a wide range of adverse health effects, ranging from simple irritation to systemic diseases. It has been shown that VOCs could also influence immune system. Despite significant achievements in the risk assessment of VOCs, the toxicological assessment model, remains limited, particularly for studying the effect of VOCs on immune system.

The procedure to obtain high-resolution 2D gels has been established with protein extracts from Jurkat T cells. Alterations of the protein expression of unstimulated and stimulated Jurkat cells were being carried out upon the exposure of sublethal concentrations of benzo (a) pyrene, a well documented polycyclic aromatic hydrocarbon linked to cancer.

For validation of the results from the cellular model T cells will be differientiated from isoltatd PBMCs. The PBMC will be purified by using a cell purification kit from Milteny Biotec. This procedure allows a purity of human T cells with more than 95% purity.

 
2D gel of jurkat unstimulated cells

Figure 2D gel of unstimulated human Jurkat T cells

 

It is very important to unravel the network of proteins and the pathways involved to identify the early candidate, which can act as an indicator for the onset of the toxic effect of VOCs on the cell. Thus a list of up and down regulated proteins is further used to investigate the direct relationship between the proteins, their relationship with the pathways of the cells and their interacting nature using the online databases MINT, STRING and IntAct. Reactome and KEGG databases are used to understand the involvement of these proteins in the different metabolic and signaling pathways of the cell. Validation of the protein interaction data is carried out with the software, Pathwaystudio, which derives the information from the experimental and literature evidences from the available databases

The study is carried out in close cooperation with the Department of Environmental Immunology.

publications

Kliemt S, Lange C, Otto W, Hintze V, Möller S, von Bergen M, Hempel U, Kalkhof S.
Sulfated hyaluronan containing collagen matrices enhance cell-matrix-interaction, endocytosis, and osteogenic differentiation of human mesenchymal stromal cells.
J Proteome Res. 2012 Nov 21. [Epub ahead of print] PMID:23170904

Haange SB, Oberbach A, Schlichting N, Hugenholtz F, Smidt H, von Bergen M, Till H, Seifert J.
Metaproteome analysis and molecular genetics of rat intestinal microbiota reveals section and localisation resolved species distribution and enzymatic functionalities.
J Proteome Res. 2012 Nov 2;11(11):5406-17. PMID: 23016992

Müller SA, van der Smissen A, von Feilitzsch M, Anderegg U, Kalkhof S, von Bergen M.
Quantitative proteomics reveals altered expression of extracellular matrix related proteins of human primary dermal fibroblasts in response to sulfated hyaluronan and collagen applied as artificial extracellular matrix.
J Mater Sci Mater Med. 2012 Dec;23(12):3053-65. PMID: 22990618

Goettsch C, Kliemt S, Sinningen K, von Bergen M, Hofbauer LC, Kalkhof S.
Quantitative proteomics reveals novel functions of osteoclast-associated receptor in STAT signaling and cell adhesion in human endothelial cells.
J Mol Cell Cardiol. 2012 Dec;53(6):829-37. PMID: 22985931

Salbach J, Kliemt S, Rauner M, Rachner TD, Goettsch C, Kalkhof S, von Bergen M, Möller S, Schnabelrauch M, Hintze V, Scharnweber D, Hofbauer LC.
The effect of the degree of sulfation of glycosaminoglycans on osteoclast function and signaling pathways.
Biomaterials 2012 Nov;33(33):8418-29. PMID: 22954516

Guazzaroni ME, Herbst FA, Lores I, Tamames J, Peláez AI, López-Cortés N, Alcaide M, Del Pozo MV, Vieites JM, von Bergen M, Gallego JL, Bargiela R, López-López A, Pieper DH, Rosselló-Móra R, Sánchez J, Seifert J, Ferrer M.
Metaproteogenomic insights beyond bacterial response to naphthalene exposure and bio-stimulation.
ISME J. 2012 Jul 26. doi: 10.1038/ismej.2012.82.[Epub ahead of print] PMID: 22832345

Taubert M, Vogt C, Wubet T, Kleinsteuber S, Tarkka MT, Harms H, Buscot F, Richnow HH, von Bergen M, Seifert J
Protein-SIP enables time-resolved analysis of the carbon flux in a sulfate-reducing, benzene-degrading microbial consortium.
ISME J. 2012 Jul 12. doi: 10.1038/ismej.2012.68. [Epub ahead of print] PMID: 22791237.


Boll K, Reiche K, Kasack K, Mörbt N, Kretzschmar AK, Tomm JM, Verhaegh G, Schalken J, von Bergen M, Horn F, Hackermüller J.
MiR-130a, miR-203 and miR-205 jointly repress key oncogenic pathways and are downregulated in prostate carcinoma.
Oncogene. 2012 Mar 5. doi: 10.1038/onc.2012.55. [Epub ahead of print] PubMed PMID: 22391564.


Haas S, Jahnke HG, Moerbt N, von Bergen M, Aharinejad S, Andrukhova O, Robitzki AA
DIGE proteome analysis reveals suitability of ischemic cardiac in vitro model for studying cellular response to acute ischemia and regeneration.
PLoS One. 2012;7(2):e31669. Epub 2012 Feb 22. PubMed PMID: 22384053