Publikationsdatum:
2004-07-13
Beschreibung:
Erythropoietin (EPO) is both hematopoietic and tissue protective, putatively through interaction with different receptors. We generated receptor subtype-selective ligands allowing the separation of EPO's bioactivities at the cellular level and in animals. Carbamylated EPO (CEPO) or certain EPO mutants did not bind to the classical EPO receptor (EPOR) and did not show any hematopoietic activity in human cell signaling assays or upon chronic dosing in different animal species. Nevertheless, CEPO and various nonhematopoietic mutants were cytoprotective in vitro and conferred neuroprotection against stroke, spinal cord compression, diabetic neuropathy, and experimental autoimmune encephalomyelitis at a potency and efficacy comparable to EPO.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leist, Marcel -- Ghezzi, Pietro -- Grasso, Giovanni -- Bianchi, Roberto -- Villa, Pia -- Fratelli, Maddalena -- Savino, Costanza -- Bianchi, Marina -- Nielsen, Jacob -- Gerwien, Jens -- Kallunki, Pekka -- Larsen, Anna Kirstine -- Helboe, Lone -- Christensen, Soren -- Pedersen, Lars O -- Nielsen, Mette -- Torup, Lars -- Sager, Thomas -- Sfacteria, Alessandra -- Erbayraktar, Serhat -- Erbayraktar, Zubeyde -- Gokmen, Necati -- Yilmaz, Osman -- Cerami-Hand, Carla -- Xie, Qiao-Wen -- Coleman, Thomas -- Cerami, Anthony -- Brines, Michael -- New York, N.Y. -- Science. 2004 Jul 9;305(5681):239-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉H. Lundbeck A/S, 2500 Valby, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15247477" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
Animals
;
Apoptosis
;
Binding Sites
;
Cells, Cultured
;
Diabetic Neuropathies/drug therapy
;
Drug Design
;
Encephalomyelitis, Autoimmune, Experimental/drug therapy
;
Erythropoiesis
;
Erythropoietin/*analogs &
;
derivatives/chemistry/genetics/metabolism/pharmacology/*therapeutic use
;
Female
;
Hematocrit
;
Humans
;
Ligands
;
Mice
;
Mice, Inbred C3H
;
Mutagenesis
;
Nervous System Diseases/*drug therapy
;
Neurons/metabolism
;
Neuroprotective Agents/chemistry/metabolism/pharmacology/*therapeutic use
;
Rats
;
Rats, Sprague-Dawley
;
Receptors, Erythropoietin/metabolism
;
Recombinant Proteins
;
Signal Transduction
;
Spinal Cord Compression/drug therapy
;
Stroke/drug therapy
;
Structure-Activity Relationship
Print ISSN:
0036-8075
Digitale ISSN:
1095-9203
Thema:
Biologie
,
Chemie und Pharmazie
,
Informatik
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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