Abstract
The discovery of endogenous bioactive peptides has typically required a lengthy identification process. Computer-assisted analysis of cDNA and genomic DNA sequence information can markedly shorten the process. A bioinformatic analysis of full-length, enriched human cDNA libraries searching for previously unidentified bioactive peptides resulted in the identification and characterization of two related peptides of 28 and 20 amino acids, which we designated salusin-α and salusin-β. Salusins are translated from an alternatively spliced mRNA of TOR2A, a gene encoding a protein of the torsion dystonia family. Intravenous administration of salusin-α or salusin-β to rats causes rapid, profound hypotension and bradycardia. Salusins increase intracellular Ca2+, upregulate a variety of genes and induce cell mitogenesis. Salusin-β stimulates the release of arginine-vasopressin from rat pituitary. Expression of TOR2A mRNA and its splicing into preprosalusin are ubiquitous, and immunoreactive salusin-α and salusin-β are detected in many human tissues, plasma and urine, suggesting that salusins are endocrine and/or paracrine factors.
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Acknowledgements
We thank members of the Tokyo Research Laboratories and the Pharmaceutical Research Institute of Kyowa Hakko Kogyo Co. Ltd; K. Shibata and M. Koike for peptide design and synthesis; K. Sasaki for priceless comments and critical reviews; A. Yoshimatsu and S. Shirakura for studies of isolated blood vessels; K. Kurata-Miura for conventional RT-PCR; H. Kawai for sequence analysis; and A. Furuya for advice. We thank S.H. Yamaguchi and H. Yasuda for technical assistance; K. Ishizaka and H. Tanaka for surgically resected tissues; and K.D. Hanson for critical reviews and valuable feedback with constructive comments. This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas (C) 'Medical Genome Science', and a Grant-in-Aid for Scientific Research (B) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, both to M.S.
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Shichiri, M., Ishimaru, S., Ota, T. et al. Salusins: newly identified bioactive peptides with hemodynamic and mitogenic activities. Nat Med 9, 1166–1172 (2003). https://doi.org/10.1038/nm913
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DOI: https://doi.org/10.1038/nm913
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