Lanthanum chloride precipitation-based toxicoproteomic analysis of 3-monochloropropane-1,2-diol toxicity in rat kidney reveals involvement of extracellular signal-regulated kinase 2

Oberemm A, Braun M, Sawada S, Pink M, Frenzel F, Rozycki C, Meckert C, Zabinsky E, Braeuning A, Lampen A (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Archives of Toxicology Springer Verlag (Germany)

Book Volume: 91

Pages Range: 3247-3260

Journal Issue: 10

DOI: 10.1007/s00204-017-1959-0

Abstract

The heat-induced food contaminant 3-monochloropropane-1,2-diol (3-MCPD) and its fatty acid esters exert nephrotoxicity in rodents. Previous studies including a non-targeted toxicoproteomics approach using samples from a 28-day oral toxicity study in rats with 10 mg/kg body weight (b.w.) of 3-MCPD, an equimolar dose of 53 mg/kg b.w. 3-MCPD dipalmitate and a lower dose of 13.3 mg/kg b.w. of 3-MCPD dipalmitate, revealed substance-induced alterations in metabolic pathways, especially for glycolysis and energy metabolism. In order to obtain deeper insight into mechanisms of 3-MCPD toxicity, samples from the above-mentioned study were reanalyzed using a lanthanum chloride precipitation-based toxicoproteomics approach in order to increase the yield of phosphorylated proteins, crucial players in cellular signaling. A comparison of standard 2D-gel-based proteomics and lanthanum chloride precipitation was performed, thus providing a comprehensive case study on these two methods using in vivo effects of an important food toxicant in a primary target organ. While resulting in similar 2D-gel electrophoresis pherograms and spot counts, data analysis demonstrated that lanthanum precipitation yielded more significantly deregulated proteins thus considerably improving our knowledge on 3-MCPD-dependent proteomic alterations in the kidney. 3-MCPD-induced deregulation of the phosphorylated, active version of extracellular signal-regulated kinase 2 (ERK2) in rat kidney was demonstrated using mass spectrometry and immunohistochemistry. In summary, this paper for the first time links 3-MCPD effects to deregulation of the ERK/mitogen-activated protein kinase signaling pathway in rat kidney and demonstrates that lanthanum chloride precipitation is suited to support the gain of mechanistic knowledge on organ toxicity using 2D-gel-based proteomics.

Authors with CRIS profile

Mario Pink Lehrstuhl für Arbeits-, Sozial- und Umweltmedizin

Involved external institutions

Bundesinstitut für Risikobewertung (BfR) DE Germany (DE) Eberhard Karls Universität Tübingen DE Germany (DE)

How to cite

APA:

Oberemm, A., Braun, M., Sawada, S., Pink, M., Frenzel, F., Rozycki, C.,... Lampen, A. (2017). Lanthanum chloride precipitation-based toxicoproteomic analysis of 3-monochloropropane-1,2-diol toxicity in rat kidney reveals involvement of extracellular signal-regulated kinase 2. Archives of Toxicology, 91(10), 3247-3260. https://doi.org/10.1007/s00204-017-1959-0

MLA:

Oberemm, Axel, et al. "Lanthanum chloride precipitation-based toxicoproteomic analysis of 3-monochloropropane-1,2-diol toxicity in rat kidney reveals involvement of extracellular signal-regulated kinase 2." Archives of Toxicology 91.10 (2017): 3247-3260.

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