Lanthanum chloride precipitation-based toxicoproteomic analysis of 3-monochloropropane-1,2-diol toxicity in rat kidney reveals involvement of extracellular signal-regulated kinase 2
Autor: | Axel Oberemm, Christel Rozycki, C. Meckert, Alfonso Lampen, Stefanie Sawada, Mario Pink, Monique Braun, Albert Braeuning, Falko Frenzel, Elke Zabinsky |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Male Proteomics Health Toxicology and Mutagenesis alpha-Chlorohydrin Toxicology Kidney Nephrotoxicity 03 medical and health sciences 0404 agricultural biotechnology In vivo Lanthanum Toxicity Tests Extracellular Animals Chemical Precipitation Electrophoresis Gel Two-Dimensional Phosphorylation Rats Wistar Protein kinase A Mitogen-Activated Protein Kinase 1 Kinase Chemistry 04 agricultural and veterinary sciences General Medicine 040401 food science Metabolic pathway 030104 developmental biology Biochemistry Toxicity Signal transduction |
Zdroj: | Archives of toxicology. 91(10) |
ISSN: | 1432-0738 |
Popis: | 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. |
Databáze: | OpenAIRE |
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