Universitätsbibliothek Wien

Untersuchung zur Rolle des klassischen Erythropoietin-Rezeptors bei der Frataxin erhöhenden Wirkung von rekombinantem humanem Erythropoietin

Helminger, Melissa (2008) Untersuchung zur Rolle des klassischen Erythropoietin-Rezeptors bei der Frataxin erhöhenden Wirkung von rekombinantem humanem Erythropoietin.
Diplomarbeit, University of Vienna. Fakultät für Lebenswissenschaften
BetreuerIn: Goldenberg, Hans
Gesperrt bis: 7 November 2010

[img]
Preview
PDF
Alle Rechte vorbehalten / All rights reserved

Download (2123Kb)
URN: urn:nbn:at:at-ubw:1-29623.96947.980460-0

Link zu u:search

Abstract in German

nicht angegeben

Schlagwörter in Deutsch

Rekombinates humanes Erythropoietin / K562 Zellen / THP1 Zellen / EPO-Rezeptor

Abstract in English

Background: Friedreich's ataxia (FRDA) is a neurodegenerative disorder caused by decreased expression of the mitochondrial protein frataxin, described to be an iron chaperone for the assembly of iron-sulfur clusters in the mitrochondria causing iron accumulation in mitochondria, oxidative stress and cell damage. Recently we showed that recombinant human erythropoietin (rhuEPO) significantly increases frataxin expression by a still unknown mechanism. In this study we investigate the role of the classical erythropoietin receptor (EPO-R) in the frataxin- increasing effect of rhuEPO Materials and Methods: Expression of the EPO-R in human erythroleukaemic K562 cells and human monocytes THP-1 cells was detected by western blot. In the experiments K562-cells, THP-1-cells as well as primary lymphocytes from control and FRDA patients were incubated with different concentrations of rhuEPO. Frataxin expression was detected by an electrochemical luminescence assay (ECLIA) and real-time RT-PCR for frataxin-mRNA. Results: Western blot analysis confirmed expression of EPO-R in K562 cells, but complete absence of EPO-R expression in THP-1 cells. However the increase in frataxin protein expression following treatment with rhuEPO correlated with the concentration of rhuEPO used in both cell lines, comparable to the effect of rhuEPO on frataxin expression in primary lymphocytes from control and FRDA patients. RhuEPO increased frataxin expression without increasing frataxin-mRNA. Discussion: We investigated if the frataxin increasing effect of rhuEPO is mediated via the classical EPO-R. To test if EPO binding to the classical EPO-R is an essential step to mediate EPO`s effect on frataxin-expression we used two cell culture models: one expressing the classical EPO-R, the erythroleukaemic K562 cells and a cell line not expressing this receptor, human monocyte THP-1 cells. We found that rhuEPO increased frataxin expression in both cell lines, which indicates that the effect of rhuEPO on frataxin expression is not limited to cells expressing the classical EPO-R. RhuEPO had no effect on frataxin mRNA suggesting that the observed increase in frataxin protein is attributable to a posttranslational mechanism. Conclusion: RhuEPO increases frataxin expression by a mechanism without involvement of the classical EPO-R. The results of this study provide a scientific basis to further examine the effectiveness of non-erythropoietic EPO-derivatives which do not bind to the classical EPO-R as a possible treatment option for FRDA patients.

Item Type: Hochschulschrift (Diplomarbeit)
Author: Helminger, Melissa
Title: Untersuchung zur Rolle des klassischen Erythropoietin-Rezeptors bei der Frataxin erhöhenden Wirkung von rekombinantem humanem Erythropoietin
Umfangsangabe: 137 S. : Ill., graph. Darst.
Institution: University of Vienna
Faculty: Fakultät für Lebenswissenschaften
Publication year: 2008
Language: ger ... Deutsch
Supervisor: Goldenberg, Hans
Assessor: Goldenberg, Hans
Classification: 35 Chemie > 35.79 Biochemie: Sonstiges
30 Naturwissenschaften allgemein > 30.99 Naturwissenschaften allgemein: Sonstiges
AC Number: AC07115822
Item ID: 3017
(Das PDF-Layout ist ident mit der Druckausgabe der Hochschulschrift.)

Urheberrechtshinweis: Für Dokumente, die in elektronischer Form über Datennetze angeboten werden, gilt uneingeschränkt das österreichische Urheberrechtsgesetz; insbesondere sind gemäß § 42 UrhG Kopien und Vervielfältigungen nur zum eigenen und privaten Gebrauch gestattet. Details siehe Gesetzestext.

Edit item (Administrators only) Edit item (Administrators only)