A proteomic approach for the identification of immunotoxic properties of Tulipalin A.
The immune system is permanently exposed to several environmental influences that can have adverse effects on immune cells or organs leading to immunosuppression or inappropriate immunostimulation, called direct immunotoxicity. The natural compound Tulipalin A (TUPA), a lactone with α-methylene-γ-butyrolactone moiety, can influence the immune system and lead to allergic contact dermatitis. This in vitro study focused on effects of TUPA using two immune cell lines (Jurkat T cells and THP-1 monocytes). To evaluate the immunotoxic potential of the compound, a proteomic approach applying 2D gel electrophoresis and MALDI-TOF/TOF-MS in combination with metabolomic analysis was used after exposure of the cells to IC10of TUPA. THP-1 cells showed a strong robustness to TUPA treatment since only five proteins were altered. In contrast, in Jurkat T cells an increase in the abundance of 66 proteins and a decrease of six proteins was determined. These intracellular proteins were mapped to biological processes. Especially an accumulation of chaperones and an influence on the purine synthesis were observed. The changes in purine synthesis were confirmed by metabolomic analysis. In conclusion, the data indicate possible target processes of low doses of TUPA in Jurkat T cells and provides knowledge of how TUPA affects the functionality of immune cells.
Institute of Pharmacy, Pharmaceutical Biology, Ernst-Moritz-Arndt-University, Greifswald, Germany.
Paula
P
Zwicker
Institute of Pharmacy, Pharmaceutical Biology, Ernst-Moritz-Arndt-University, Greifswald, Germany.
Nadin
N
Schultze
Institute of Biochemistry, Biochemistry of Metabolism/Metabolomics, Ernst-Moritz-Arndt-University, Greifswald, Germany.
Sarah
S
Niehs
Institute of Biochemistry, Biochemistry of Metabolism/Metabolomics, Ernst-Moritz-Arndt-University, Greifswald, Germany.
Karen
K
Methling
Institute of Biochemistry, Biochemistry of Metabolism/Metabolomics, Ernst-Moritz-Arndt-University, Greifswald, Germany.
Martina
M
Wurster
Institute of Microbiology, Microbial Physiology and Molecular Biology, Ernst-Moritz-Arndt-University, Greifswald, Germany.
Dirk
D
Albrecht
Institute of Microbiology, Microbial Physiology and Molecular Biology, Ernst-Moritz-Arndt-University, Greifswald, Germany.
Jörg
J
Bernhardt
Institute of Microbiology, Microbial Physiology and Molecular Biology, Ernst-Moritz-Arndt-University, Greifswald, Germany.
Gerhild
G
Wachlin
Institute of Biochemistry, Biochemistry of Metabolism/Metabolomics, Ernst-Moritz-Arndt-University, Greifswald, Germany.
Michael
M
Lalk
Institute of Pharmacy, Pharmaceutical Biology, Ernst-Moritz-Arndt-University, Greifswald, Germany.
Ulrike
U
Lindequist
Institute of Pharmacy, Pharmaceutical Biology, Ernst-Moritz-Arndt-University, Greifswald, Germany.
Beate
B
Haertel
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000276:immunology / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D017449:Dermatitis, Allergic Contact / Q000209:etiology; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D055442:Metabolome; D017510:Protein Folding / Q000187:drug effects; D040901:Proteomics / Q000379:methods*; D011687:Purines / Q000096:biosynthesis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D018675:Toxicity Tests / Q000379:methods
D011687:Purines; C014096:alpha-methylene gamma-butyrolactone; D015107:4-Butyrolactone
Cell biology; Immunotoxicity; Metabolomics; OMICS; Toxicoproteomics; Tulipalin A
