| dc.description.abstract | Abstract
Degree Project thesis, Programme in Medicine, 2015.
Sara Elofsson, Department of Molecular and Clinical Medicine, Institute of Medicine,
University of Gothenburg, Sweden.
Börje Haraldsson and Johannes Elvin, supervisors.
Previous clinical studies and in vitro experiments have confirmed that treatment with
adrenocorticotropic hormone (ACTH) have ameliorating effects on nephrotic
syndrome. This action is believed to be mediated by stimulation of Melanocortin-1
Receptor (MC1R) in podocytes. The full extent of MC1R signalling in podocytes is
still unknown, but the anti-oxidative enzyme catalase has been found to be one of the
downstream effectors. We have studied in what ways catalase is regulated to exert its
action and what effect this activity has in podocytes. In addition, we studied the
human constitutively active MC1R-mutant, E94K.
Cultured differentiated mouse podocytes were transduced with different lentivirus to
overexpress MC1R or the constitutively active MC1R-mutant. The podocytes were
subjected to different concentrations of a nephrotoxic agent, puromycin, and/or the
known MC1R agonist BMS-470539. In addition, a catalase specific inhibitor, 3-
amino-1, 2, 4-triazole, was used to elucidate whether the protective effects of MC1R
stimulation is dependent on catalase. The effects due to different treatments on the
podocytes were assessed with diverse analytical assays.
The human constitutive MC1R-mutant did not show an effect in the range we
expected and the mouse mutant will be tested hereafter. The inhibitor gave a dosedependent
inhibition but had an unsuspected interaction with puromycin.
In summary, catalase still seems to have a possible role in the ameliorating effects of
MC1R-stimulation in nephrotic syndrome and these experiments have given new
strategies and developed better implements to future experiments. | sv |
