High concentrations of phenylalanine stimulate peroxisome proliferator-activated receptor gamma: Implications for the pathophysiology of phenylketonuria

Schumacher U, Lukacs Z, Kaltschmidt C, Freudlsperger C, Schulz D, Kompisch K, Mueller R, Rudolph T, Santer R, Lorke DE, Ullrich K (2008)
NEUROBIOLOGY OF DISEASE 32(3): 385-390.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
Download
Es wurden keine Dateien hochgeladen. Nur Publikationsnachweis!
DOI
Autor*in
Schumacher, Udo; Lukacs, Zoltan; Kaltschmidt, ChristianUniBi; Freudlsperger, Christian; Schulz, Dorothea; Kompisch, Kai; Mueller, Reinhard; Rudolph, Tanja; Santer, Rene; Lorke, Dietrich E.; Ullrich, Kurt
Einrichtung
Fakultät für Biologie > Zellbiologie der Tiere
Centrum für Biotechnologie > Arbeitsgruppe C. Kaltschmidt
Centrum für Biotechnologie > Institut für Genomforschung und Systembiologie
Abstract / Bemerkung
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 PPAR gamma 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 PPAR gamma 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. (C) 2008 Elsevier Inc. All rights reserved.
Stichworte
Peroxisome proliferator-activated receptor gamma; Pathophysiology; Neuroblastoma cells; Phenylketonuria
Erscheinungsjahr
2008
Zeitschriftentitel
NEUROBIOLOGY OF DISEASE
Band
32
Ausgabe
3
Seite(n)
385-390
ISSN
0969-9961
Page URI
https://pub.uni-bielefeld.de/record/1636528

Zitieren

Schumacher U, Lukacs Z, Kaltschmidt C, et al. High concentrations of phenylalanine stimulate peroxisome proliferator-activated receptor gamma: Implications for the pathophysiology of phenylketonuria. NEUROBIOLOGY OF DISEASE. 2008;32(3):385-390.
Schumacher, U., Lukacs, Z., Kaltschmidt, C., Freudlsperger, C., Schulz, D., Kompisch, K., Mueller, R., et al. (2008). High concentrations of phenylalanine stimulate peroxisome proliferator-activated receptor gamma: Implications for the pathophysiology of phenylketonuria. NEUROBIOLOGY OF DISEASE, 32(3), 385-390. https://doi.org/10.1016/j.nbd.2008.07.020
Schumacher, Udo, Lukacs, Zoltan, Kaltschmidt, Christian, Freudlsperger, Christian, Schulz, Dorothea, Kompisch, Kai, Mueller, Reinhard, et al. 2008. “High concentrations of phenylalanine stimulate peroxisome proliferator-activated receptor gamma: Implications for the pathophysiology of phenylketonuria”. NEUROBIOLOGY OF DISEASE 32 (3): 385-390.
Schumacher, U., Lukacs, Z., Kaltschmidt, C., Freudlsperger, C., Schulz, D., Kompisch, K., Mueller, R., Rudolph, T., Santer, R., Lorke, D. E., et al. (2008). High concentrations of phenylalanine stimulate peroxisome proliferator-activated receptor gamma: Implications for the pathophysiology of phenylketonuria. NEUROBIOLOGY OF DISEASE 32, 385-390.
Schumacher, U., et al., 2008. High concentrations of phenylalanine stimulate peroxisome proliferator-activated receptor gamma: Implications for the pathophysiology of phenylketonuria. NEUROBIOLOGY OF DISEASE, 32(3), p 385-390.
U. Schumacher, et al., “High concentrations of phenylalanine stimulate peroxisome proliferator-activated receptor gamma: Implications for the pathophysiology of phenylketonuria”, NEUROBIOLOGY OF DISEASE, vol. 32, 2008, pp. 385-390.
Schumacher, U., Lukacs, Z., Kaltschmidt, C., Freudlsperger, C., Schulz, D., Kompisch, K., Mueller, R., Rudolph, T., Santer, R., Lorke, D.E., Ullrich, K.: High concentrations of phenylalanine stimulate peroxisome proliferator-activated receptor gamma: Implications for the pathophysiology of phenylketonuria. NEUROBIOLOGY OF DISEASE. 32, 385-390 (2008).
Schumacher, Udo, Lukacs, Zoltan, Kaltschmidt, Christian, Freudlsperger, Christian, Schulz, Dorothea, Kompisch, Kai, Mueller, Reinhard, Rudolph, Tanja, Santer, Rene, Lorke, Dietrich E., and Ullrich, Kurt. “High concentrations of phenylalanine stimulate peroxisome proliferator-activated receptor gamma: Implications for the pathophysiology of phenylketonuria”. NEUROBIOLOGY OF DISEASE 32.3 (2008): 385-390.

5 Zitationen in Europe PMC

Daten bereitgestellt von Europe PubMed Central.

A Multiplatform Metabolomics Approach to Characterize Plasma Levels of Phenylalanine and Tyrosine in Phenylketonuria.
Blasco H, Veyrat-Durebex C, Bertrand M, Patin F, Labarthe F, Henique H, Emond P, Andres CR, Antar C, Landon C, Nadal-Desbarats L, Maillot F., JIMD Rep 32(), 2017
PMID: 27300702
Metabolome-wide association study of phenylalanine in plasma of common marmosets.
Go YM, Walker DI, Soltow QA, Uppal K, Wachtman LM, Strobel FH, Pennell K, Promislow DE, Jones DP., Amino Acids 47(3), 2015
PMID: 25526869
Transcriptome-metabolome wide association study (TMWAS) of maneb and paraquat neurotoxicity reveals network level interactions in toxicologic mechanism.
Roede JR, Uppal K, Park Y, Tran V, Jones DP., Toxicol Rep 1(), 2014
PMID: 27722094
TATN-1 mutations reveal a novel role for tyrosine as a metabolic signal that influences developmental decisions and longevity in Caenorhabditis elegans.
Ferguson AA, Roy S, Kormanik KN, Kim Y, Dumas KJ, Ritov VB, Matern D, Hu PJ, Fisher AL., PLoS Genet 9(12), 2013
PMID: 24385923
Experimental evidence that phenylalanine provokes oxidative stress in hippocampus and cerebral cortex of developing rats.
Fernandes CG, Leipnitz G, Seminotti B, Amaral AU, Zanatta A, Vargas CR, Dutra Filho CS, Wajner M., Cell Mol Neurobiol 30(2), 2010
PMID: 19774456

22 References

Daten bereitgestellt von Europe PubMed Central.

Neuropathological findings in phenyl-pyruvic oligophrenia (phenyl-ketonuria).
ALVORD EC Jr, STEVENSON LD, VOGEL FS, ENGLE RL Jr., J. Neuropathol. Exp. Neurol. 9(3), 1950
PMID: 15437204
In vitro differentiation of human processed lipoaspirate cells into early neural progenitors.
Ashjian PH, Elbarbary AS, Edmonds B, DeUgarte D, Zhu M, Zuk PA, Lorenz HP, Benhaim P, Hedrick MH., Plast. Reconstr. Surg. 111(6), 2003
PMID: 12711954
Morphologic and histoanatomic observations of the brain in untreated human phenylketonuria.
Bauman ML, Kemper TL., Acta Neuropathol. 58(1), 1982
PMID: 7136517
Differential activation of peroxisome proliferator-activated receptor-gamma by troglitazone and rosiglitazone.
Camp HS, Li O, Wise SC, Hong YH, Frankowski CL, Shen X, Vanbogelen R, Leff T., Diabetes 49(4), 2000
PMID: 10871190
Über Ausscheidung von Phenylbrenztraubensäure in den Harn als Stoffwechselanomalie in Verbindung mit Imbezillität
Fϕlling, Z. Physiol. Chem. 227(), 1934
Anti-proliferative effect of peroxisome proliferator-activated receptor gamma agonists on human malignant melanoma cells in vitro.
Freudlsperger C, Moll I, Schumacher U, Thies A., Anticancer Drugs 17(3), 2006
PMID: 16520661
Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor.
Greene LA, Tischler AS., Proc. Natl. Acad. Sci. U.S.A. 73(7), 1976
PMID: 1065897
Elevated phenylalanine levels interfere with neurite outgrowth stimulated by the neuronal cell adhesion molecule L1 in vitro.
Hartwig C, Gal A, Santer R, Ullrich K, Finckh U, Kreienkamp HJ., FEBS Lett. 580(14), 2006
PMID: 16716305
Differentiation of human neuroblastoma by phenylacetate is mediated by peroxisome proliferator-activated receptor gamma.
Han S, Wada RK, Sidell N., Cancer Res. 61(10), 2001
PMID: 11358817
The neuropathology of phenylketonuria: human and animal studies.
Huttenlocher PR., Eur. J. Pediatr. 159 Suppl 2(), 2000
PMID: 11043154
NF-kappaB regulates spatial memory formation and synaptic plasticity through protein kinase A/CREB signaling.
Kaltschmidt B, Ndiaye D, Korte M, Pothion S, Arbibe L, Prullage M, Pfeiffer J, Lindecke A, Staiger V, Israel A, Kaltschmidt C, Memet S., Mol. Cell. Biol. 26(8), 2006
PMID: 16581769
Limited tumor growth (HT29) in vivo under RO205-2349 is due to increased apoptosis and reduced cell volume but not to decreased proliferation rate.
Katoh M, Feldhaus S, Schnitzer T, Bauer S, Schumacher U., Cancer Lett. 210(1), 2004
PMID: 15172115
Characterization of elementary Ca2+ release signals in NGF-differentiated PC12 cells and hippocampal neurons.
Koizumi S, Bootman MD, Bobanovic LK, Schell MJ, Berridge MJ, Lipp P., Neuron 22(1), 1999
PMID: 10027295
The PPARgamma ligands PGJ2 and rosiglitazone show a differential ability to inhibit proliferation and to induce apoptosis and differentiation of human glioblastoma cell lines.
Morosetti R, Servidei T, Mirabella M, Rutella S, Mangiola A, Maira G, Mastrangelo R, Koeffler HP., Int. J. Oncol. 25(2), 2004
PMID: 15254749
Pioglitazone inhibits the growth of human leukemia cell lines and primary leukemia cells while sparing normal hematopoietic stem cells.
Saiki M, Hatta Y, Yamazaki T, Itoh T, Enomoto Y, Takeuchi J, Sawada U, Aizawa S, Horie T., Int. J. Oncol. 29(2), 2006
PMID: 16820887
Microarray analysis of tumor necrosis factor alpha induced gene expression in U373 human glioblastoma cells.
Schwamborn J, Lindecke A, Elvers M, Horejschi V, Kerick M, Rafigh M, Pfeiffer J, Prullage M, Kaltschmidt B, Kaltschmidt C., BMC Genomics 4(1), 2003
PMID: 14641910
The cellular response to PPARgamma ligands is related to the phenotype of neuroblastoma cell lines.
Servidei T, Morosetti R, Ferlini C, Cusano G, Scambia G, Mastrangelo R, Koeffler HP., Oncol. Res. 14(7-8), 2004
PMID: 15301425
Altered expression of myocilin in the brain of a mouse model for phenylketonuria (PKU).
Surendran S, Matalon D, Tyring SK, Rady PL, Velagaleti GV, Matalon R., Neurosci. Lett. 382(3), 2005
PMID: 15925112
Ligands for the peroxisome proliferator-activated receptor-gamma have inhibitory effects on growth of human neuroblastoma cells in vitro.
Valentiner U, Carlsson M, Erttmann R, Hildebrandt H, Schumacher U., Toxicology 213(1-2), 2005
PMID: 16009482
Medical significance of peroxisome proliferator-activated receptors.
Vamecq J, Latruffe N., Lancet 354(9173), 1999
PMID: 10408502
Peroxisome proliferator-activated receptor gamma-mediated regulation of neural stem cell proliferation and differentiation.
Wada K, Nakajima A, Katayama K, Kudo C, Shibuya A, Kubota N, Terauchi Y, Tachibana M, Miyoshi H, Kamisaki Y, Mayumi T, Kadowaki T, Blumberg RS., J. Biol. Chem. 281(18), 2006
PMID: 16524877
Autism and mental retardation: neuropathologic studies performed in four retarded persons with autistic behavior.
Williams RS, Hauser SL, Purpura DP, DeLong GR, Swisher CN., Arch. Neurol. 37(12), 1980
PMID: 7447762
Export

Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®
Quellen

PMID: 18755275
PubMed | Europe PMC

Suchen in

Google Scholar