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 were designated salusin- and salusin- 1.
Salusins are translated from an alternatively spliced mRNA of TOR2A, a gene encoding a protein of the torsion dystonia family 1.
Shichiri et al., reported the discovery of Salusin peptides with hemodynamic and mitogenic activities in 2003 1.
Salusin-a was predicted to be a 28-residue peptide with an amidated carboxyl-terminus, while salusin-ß was predicted to be a 20-residue peptide with a free carboxyl-terminus.
Their amino acid sequences are:
Mode of Action
Salusin-a and -ß did not directly affect cardiac function in the rat heart but that they improved calcium uptake and protein synthesis in neonatal rat cardiomyocytes through the calcium, calcineurin, MAPK and PKC signal pathways 2. Human salusin-ß is a surrogate ligand of the mouse MrgA1 and raises a cautionary flag for experiments that analyze the pharmacological profiles of mas-like G protein-coupled receptors from different species 3.
Intravenous administration of salusin-a or salusin-ß to rats causes rapid, profound hypotension and bradycardia. Salusins increase intracellular Ca2+, upregulate a variety of genes and induce cell mitogenesis. Salusin-ß stimulates the release of arginine-vasopressin from rat pituitary. Expression of TOR2A mRNA and its splicing into preprosalusin are ubiquitous and immunoreactive salusin-a and salusin-ß are detected in many human tissues, plasma and urine, suggesting that salusins are endocrine and/or paracrine factors 1.
1. Shichiri M, Ishimaru S, Ota T, Nishikawa T, Isogai T, Hirata Y (2003). Salusins: newly identified bioactive peptides with hemodynamic and mitogenic activities. Nat Med., 9(9):1166-1172.
2. Yu F, Zhao J, Yang J, Gen B, Wang S, Feng X, Tang C, Chang L (2004). Salusins promote cardiomyocyte growth but does not affect cardiac function in rats. Regul Pept., 122(3):191-197
3. Wang Z, Takahashi T, Saito Y, Nagasaki H, Ly NK, Nothacker HP, Reinscheid RK, Yang J, Chang JK, Shichiri M, Civelli O (2006). Salusin ß is a surrogate ligand of the mas-like G protein-coupled receptor MrgA1. Eur J Pharmacol., 539(3):145-150.
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