Incorporation of Ortho- and Meta-Tyrosine Into Cellular Proteins Leads to Erythropoietin-Resistance in an Erythroid Cell Line
| Autor: | István Wittmann, Gergő A. Molnár, Szilárd Kun, Esztella Mikolás, Eszter Sélley, Tamás Kőszegi, Boglárka Laczy |
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| Rok vydání: | 2013 |
| Předmět: |
MAPK/ERK pathway
Cell signaling lcsh:Diseases of the circulatory (Cardiovascular) system MAP Kinase Signaling System Drug Resistance Erythropoietin-resistance lcsh:RC870-923 Cell Line Erythroid Cells Western blot hemic and lymphatic diseases lcsh:Dermatology STAT5 Transcription Factor medicine Humans Erythropoietin STAT5 Cell Proliferation biology medicine.diagnostic_test Proteins General Medicine lcsh:RL1-803 lcsh:Diseases of the genitourinary system. Urology Recombinant Proteins Epoetin Alfa Tyrosine isomers Biochemistry Oxidative stress lcsh:RC666-701 Nephrology Cell culture biology.protein Tyrosine Phosphorylation Cardiology and Cardiovascular Medicine Intracellular Signal Transduction medicine.drug |
| Zdroj: | Kidney & Blood Pressure Research, Vol 38, Iss 2-3, Pp 217-225 (2014) |
| ISSN: | 1423-0143 1420-4096 |
| Popis: | Background/Aims: Erythropoietin-resistance is an unsolved concern in the treatment of renal anaemia. We aimed to investigate the possible role of ortho- and meta-tyrosine - the hydroxyl free radical products of L-phenylalanine - in the development of erythropoietin-resistance. Methods: TF-1 erythroblast cell line was used. Cell concentration was determined on day 1; 2 and 3 by two independent observers simultaneously in Bürker cell counting chambers. Protein concentration was determined with colorimetric method. Para-, ortho- and meta-tyrosine levels were measured using reverse phase-HPLC with fluorescence detection. Using Western blot method activating phosphorylation of STAT5 and ERK1/2 were investigated. Results: We found a time- and concentration-dependent decrease of erythropoietin-induced proliferative activity in case of ortho- and meta-tyrosine treated TF-1 erythroblasts, compared to the para-tyrosine cultured cells. Decreased erythropoietin-response could be regained with a competitive dose of para-tyrosine. Proteins of erythroblasts treated by ortho- or meta-tyrosine had lower para-tyrosine and higher ortho- or meta-tyrosine content. Activating phosphorylation of ERK and STAT5 due to erythropoietin was practically prevented by ortho- or meta-tyrosine treatment. Conclusion: According to this study elevated ortho- and meta-tyrosine content of erythroblasts may lead to the dysfunction of intracellular signaling, resulting in erythropoietin-hyporesponsiveness. |
| Databáze: | OpenAIRE |
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