Autocrine proliferative effect of ghrelin on leukemic HL-60 and THP-1 cells.
Ghrelin is a 28 amino acid peptide hormone that is mainly produced by the stomach, but also by several tissues and tumors. Ghrelin is octanoylated on the Ser(3), but is also detected as a des-acylated form. Only the acylated ghrelin activates the GH secretagogue receptor (GHS-R) type 1a to stimulate GH release, and regulate food intake and energy metabolism. For the first time, we report that ghrelin and des-acyl ghrelin are present in human promyelocytic HL-60, monocytic THP-1 and lymphoblastic SupT1 cell lines. The human leukemic cell lines did not express the functional GHS-R 1a, whereas they expressed GHS-R 1b, a truncated variant of the receptor. Leukemic cell proliferation was not modified by the addition of octanoylated or des-acyl ghrelins. However, THP-1 and HL-60 cell proliferations were inhibited by SB801, an antibody directed against the N-terminal octanoylated portion of ghrelin, suggesting that octanoylated ghrelin stimulates cell proliferation via an autocrine pathway involving an as yet unidentified ghrelin receptor. Both octanoylated and des-acyl ghrelins did not alter the basal adenylate cyclase activity. Treatments of THP-1 and SupT1 cells by both octanoylated and des-acyl ghrelins did not modify the adenylate cyclase activity in response to vasoactive intestinal peptide, suggesting that ghrelin is unlikely to modulate the anti-inflammatory and differentiating properties of vasoactive intestinal peptide.
De Vriese
Carine
C
Department of Biochemistry and Nutrition, Faculty of Medicine, Université Libre de Bruxelles, Bat G/E, CP 611, B-1070 Brussels, Belgium.
Delporte
Christine
C
D000262:Adenylyl Cyclases / Q000378:metabolism; D019898:Autocrine Communication; D043182:Carboxylesterase / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D054439:Ghrelin; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000378:metabolism / Q000473:pathology*; D007945:Leukemia, Lymphoid / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007948:Leukemia, Monocytic, Acute / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D036361:Peptide Hormones / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D043562:Receptors, G-Protein-Coupled / Q000032:analysis / Q000378:metabolism; D054440:Receptors, Ghrelin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D054439:Ghrelin; D036361:Peptide Hormones; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; C422650:ghrelin, des-n-octanoyl; D014660:Vasoactive Intestinal Peptide; D043182:Carboxylesterase; D000262:Adenylyl Cyclases