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Untersuchung zur Rolle des klassischen Erythropoietin-Rezeptors bei der Frataxin erhöhenden Wirkung von rekombinantem humanem Erythropoietin
Melissa Helminger
Art der Arbeit
Diplomarbeit
Universität
Universität Wien
Fakultät
Fakultät für Lebenswissenschaften
Betreuer*in
Hans Goldenberg
URN
urn:nbn:at:at-ubw:1-29623.96947.980460-0
Link zu u:search
(Print-Exemplar eventuell in Bibliothek verfügbar)
Abstracts
Abstract
(Deutsch)
nicht angegeben
Abstract
(Englisch)
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.
Schlagwörter
Schlagwörter
(Deutsch)
Rekombinates humanes Erythropoietin K562 Zellen THP1 Zellen EPO-Rezeptor
Autor*innen
Melissa Helminger
Haupttitel (Deutsch)
Untersuchung zur Rolle des klassischen Erythropoietin-Rezeptors bei der Frataxin erhöhenden Wirkung von rekombinantem humanem Erythropoietin
Publikationsjahr
2008
Umfangsangabe
137 S. : Ill., graph. Darst.
Sprache
Deutsch
Beurteiler*in
Hans Goldenberg
Klassifikationen
30 Naturwissenschaften allgemein > 30.99 Naturwissenschaften allgemein: Sonstiges ,
35 Chemie > 35.79 Biochemie: Sonstiges
AC Nummer
AC07115822
Utheses ID
2629
Studienkennzahl
UA | 474 | | |