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Salusins: newly identified bioactive peptides with hemodynamic and mitogenic activities

Nature Medicine volume 9, pages 1166–1172 (2003)Cite this article

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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Figure 1: Schematic representation of TOR2A, preprosalusin mRNA, and the preprosalusin, prosalusin, salusin-α(29Gly), salusin-α and salusin-β proteins.
Figure 2: Mitogenic activity of salusins.
Figure 3: Effects of intravenous administration of salusins on MAP and heart rate.
Figure 4: AVP release from perifused rat pituitaries as a function of salusin-β concentration.
Figure 5: Expression of preprosalusin in human tissues and cells.
Figure 6: Presence of salusin-like immunoreactivity in human tissues, plasma and urine, as well as supernatant from cells transfected with preprosalusin cDNA.

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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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Authors and Affiliations

  1. Tokyo Medical and Dental University Medical Hospital, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan

    Masayoshi Shichiri

  2. Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan

    Shinya Ishimaru & Yukio Hirata

  3. Helix Research Institute, Incorporated, 1532-3 Yana, Kisarazu, Chiba, 292-0812, Japan

    Toshio Ota, Tetsuo Nishikawa & Takao Isogai

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  1. Masayoshi Shichiri
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Correspondence to Masayoshi Shichiri.

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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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