Characterization of adrenomedullin in non-human primates.
Adrenomedullin (AM) is a 52 amino acid peptide involved in the pathophysiology of several human diseases. Here we show the gene structure, organ distribution, and regulated expression of AM in monkey. The monkey AM (mAM) gene is located on the short arm of chromosome 9 and it codes for a 185 amino acid preprohormone, which contains two amidated peptides identical to the human AM and proadrenomedullin N-terminal 20 peptide. The promoter region of the mAM gene contains a variety of transcription factor binding motifs. mAM is widely expressed throughout many organs as shown by real-time PCR and immunohistochemical techniques, and we have found similar levels of circulating plasma AM in monkeys and humans. A significant upregulation of the mAM mRNA was observed in monkey cells exposed to low oxygen tension conditions, TGF-beta1, all-trans-retinoic acid, and dexamethasone. Our collective data show a high degree of homology between mAM and hAM, which renders the monkey an attractive animal model for future pharmacological and pre-clinical studies targeting AM.
Zudaire
Enrique
E
Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. zudairee@mail.nih.gov
Martínez
Alfredo
A
Ozbun
Laurent L
LL
Cuttitta
Frank
F
D053607:Adrenomedullin; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D010455:Peptides / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D011323:Primates / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D014212:Tretinoin / Q000494:pharmacology
D010455:Peptides; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053607:Adrenomedullin; D014212:Tretinoin; D003907:Dexamethasone; D004247:DNA