ECE2007 Oral Communications Obesity & metabolism (7 abstracts)
Restoration of signalling capabilities in total loss of function MC4R mutations
Harald Brumm 1 , Florian Bolze 2 , Susann Friedel 3 , Anke Hinney 3 , Martin Klingenspor 2 , Johannes Hebebrand 3 , Annette Grüters 1 & Heike Biebermann 1
1Charité Universitätsmedizin Berlin, Inst. Exp. Ped. Endocrinology, Berlin, Germany; 2Phillipps-Universität, Inst. Biologie/Tierphysiologie, Marburg, Germany; 3Rheinische Kliniken Essen, Universität Duisburg Essen, Klinik für Psychiatrie und Psychotherapie des Kinder- und Jugendalters, Essen, Germany.
Objectives: The melanocortin 4 receptor (MC4R) belonging to the large superfamily of G-protein coupled receptors plays a crucial role in hypothalamic weight regulation. In approximately 3–5% of investigated obese patients inactivating MC4R mutations are the underlying molecular cause for early onset obesity. Functional characterisation revealed for specific partial loss of function MC4R mutations that restoration of receptor function is possible by usage of highly potent MC4R analogs. The analogue NDP-α-MSH is capable to restore wild type signalling in some cases of partial loss of function. However, for total loss of function receptors this procedure is insufficient.
Methods: To prove functional restoration cell surface expression was determined by cell a surface ELISA approach with N-terminal HA-tagged mutant MC4R. Signalling was determined by cAMP measurement with radioisotope labelled adenine.
Results: In the present study we set out to investigate the restoration of specific total loss of function mutations by usage of bioactive agents. We are able to show that in dependence of the location and the kind of the mutation a functional rescue is possible to different degrees.
Conclusion: This study is the first to show that in vitro restoration of signalling properties in total loss of function MC4R is possible.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more