This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fricke, K. Articles by Maronde, E. Search for Related Content PubMed PubMed Citation Articles by Fricke, K. Articles by Maronde, E.

Isolation and Characterization of a Novel Proopiomelanocortin-Derived Peptide from Hemofiltrate of Chronic Renal Failure Patients

IPF PharmaCeuticals GmbH, D-30625 Hannover, Germany

Address all correspondence and requests for reprints to: Dr. Erik Maronde, IPF PharmaCeuticals GmbH, Feodor Lynen Strasse 31, D-30625 Hannover, Germany. E-mail: erik.maronde{at}ipf-pharmaceuticals.de.

We report the isolation of a novel human circulating proopiomelanocortin-derived peptide, VA-ß-MSH, from hemofiltrate and its pharmacological characterization. Screening for lipolytic activity in differentiated 3T3-L1 adipocytes led to the isolation from a hemofiltrate peptide library by alternating reverse phase and cation exchange chromatography. In the course of this isolation, we also identified human ß-MSH-(1–22). We synthesized VA-ß-MSH by the N-(9-fluorenyl)-methoxycarbonyl (F-moc) solid phase method and used synthetic ß-MSH-(1–22) to confirm that both isolated peptides are lipolytically active in a dose-dependent manner in differentiated 3T3-L1 adipocytes in the nanomolar range. Using cAMP ELISA, we demonstrate that stimulation with both peptides caused a strong cAMP elevation in this cell system. Furthermore, we show that the selective inhibitors of cAMP-dependent protein kinase, 8-(4-Chlorophenylthio)adenosine-3',5'-cyclic monophosphorothioate, Rp-isomer (Rp-8-CPT-cAMPS); N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H89), significantly reduce VA-ß-MSH- and ß-MSH-(1–22)-mediated lipolysis. Although isolated after its lipolytic activity on 3T3-L1 cells, this newly identified circulating human melanocortin may serve other functions in human physiology. Moreover, the fact that these peptides have been identified after a functional assay, but have been overseen in large proteomic approaches, underscores the importance of such approaches in identifying previously undescribed circulating bioactive molecules.

This article has been cited by other articles:

				D. Fliser, J. Novak, V. Thongboonkerd, A. Argiles, V. Jankowski, M. A. Girolami, J. Jankowski, and H. Mischak Advances in Urinary Proteome Analysis and Biomarker Discovery J. Am. Soc. Nephrol., April 1, 2007; 18(4): 1057 - 1071. [Abstract] [Full Text] [PDF]