Salusins: newly identified bioactive peptides with hemodynamic and mitogenic activities.
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-alpha and salusin-beta. Salusins are translated from an alternatively spliced mRNA of TOR2A, a gene encoding a protein of the torsion dystonia family. Intravenous administration of salusin-alpha or salusin-beta to rats causes rapid, profound hypotension and bradycardia. Salusins increase intracellular Ca2+, upregulate a variety of genes and induce cell mitogenesis. Salusin-beta stimulates the release of arginine-vasopressin from rat pituitary. Expression of TOR2A mRNA and its splicing into preprosalusin are ubiquitous, and immunoreactive salusin-alpha and salusin-beta are detected in many human tissues, plasma and urine, suggesting that salusins are endocrine and/or paracrine factors.
Shichiri
Masayoshi
M
Tokyo Medical and Dental University Medical Hospital, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. mshichiri.cme@tmd.ac.jp
Ishimaru
Shinya
S
Ota
Toshio
T
Nishikawa
Tetsuo
T
Isogai
Takao
T
Hirata
Yukio
Y
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D000465:Algorithms; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008934:Mitogens / Q000494:pharmacology*; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D010455:Peptides / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D000251:Adenosine Triphosphatases; D000959:Antihypertensive Agents; D002118:Calcium; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008934:Mitogens; D018832:Molecular Chaperones; D010455:Peptides; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); C108175:TOR1A protein, human; C478739:TOR2A protein, human; C491549:Tor1a protein, rat