High concentrations of phenylalanine stimulate peroxisome proliferator-activated receptor gamma: implications for the pathophysiology of phenylketonuria.
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High concentrations of phenylalanine stimulate peroxisome proliferator-activated receptor gamma: implications for the pathophysiology of phenylketonuria. / Schumacher, Udo; Lukacs, Zoltan; Kaltschmidt, Christian; Freudlsperger, Christian; Schulz, Dorothea; Kompisch, Kai; Müller, Reinhard; Rudolph, Tanja Katharina; Santer, René; Lorke, Dietrich; Ullrich, Kurt.
in: NEUROBIOL DIS, Jahrgang 32, Nr. 3, 3, 2008, S. 385-390.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - High concentrations of phenylalanine stimulate peroxisome proliferator-activated receptor gamma: implications for the pathophysiology of phenylketonuria.
AU - Schumacher, Udo
AU - Lukacs, Zoltan
AU - Kaltschmidt, Christian
AU - Freudlsperger, Christian
AU - Schulz, Dorothea
AU - Kompisch, Kai
AU - Müller, Reinhard
AU - Rudolph, Tanja Katharina
AU - Santer, René
AU - Lorke, Dietrich
AU - Ullrich, Kurt
PY - 2008
Y1 - 2008
N2 - If left untreated, the common inherited metabolic disorder phenylketonuria (PKU) presents with mental retardation and reduced brain weight. The underlying molecular reasons for these deficits are unknown so far. Using human neuroblastoma cells as a model for normal human neuroblasts, elevated phenylalanine concentrations suppressed proliferation of these cells in culture. Furthermore, microarray and functional assays of these cells revealed that both phenylalanine and the known PPARgamma agonist rosiglitazone regulated the same set of genes causing subsequently similar changes in the functional assays. The lowered brain weight of PKU patients may thus be the result of reduced neuroblast proliferation caused by phenylalanine-induced stimulation of PPARgamma receptors. The observation that high concentrations of small substrates can activate receptors may serve as a new paradigm for other metabolic diseases and provides a new approach for the treatment of these disorders by application of specific receptor antagonists.
AB - If left untreated, the common inherited metabolic disorder phenylketonuria (PKU) presents with mental retardation and reduced brain weight. The underlying molecular reasons for these deficits are unknown so far. Using human neuroblastoma cells as a model for normal human neuroblasts, elevated phenylalanine concentrations suppressed proliferation of these cells in culture. Furthermore, microarray and functional assays of these cells revealed that both phenylalanine and the known PPARgamma agonist rosiglitazone regulated the same set of genes causing subsequently similar changes in the functional assays. The lowered brain weight of PKU patients may thus be the result of reduced neuroblast proliferation caused by phenylalanine-induced stimulation of PPARgamma receptors. The observation that high concentrations of small substrates can activate receptors may serve as a new paradigm for other metabolic diseases and provides a new approach for the treatment of these disorders by application of specific receptor antagonists.
M3 - SCORING: Zeitschriftenaufsatz
VL - 32
SP - 385
EP - 390
JO - NEUROBIOL DIS
JF - NEUROBIOL DIS
SN - 0969-9961
IS - 3
M1 - 3
ER -
