Salusins: newly identified bioactive peptides with hemodynamic and mitogenic activities

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-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.

Associations of serum salusin-alpha levels with atherosclerosis and left ventricular diastolic dysfunction in essential hypertension

“…It has been reported that systemic administration of salusins to rats is associated with mild hypotension and bradycardia. 7 Salusin-beta, which is theoretically synthesized concomitantly with salusin-alpha, causes profound hypotension without exerting an appreciable vasodilatory effect. The hypotensive effect of salusins is achieved partly through activation of the parasympathetic nervous system.…”

“…The hypotensive effect of salusins is achieved partly through activation of the parasympathetic nervous system. 7 As we know, elevated sympathetic nervous system activation has been shown in hypertension. So we speculate that the decreased salusin-alpha levels may lose the function to activate the parasympathetic nervous system, which resulted in shifting the autonomic balance toward the sympathetic dominant state.…”

“…5,6 Salusins are newly identified bioactive peptides discovered by bioinformatics analysis of a fulllength complememtary DNA library. 7 Shichiri et al 7 recently characterized two related peptides of 28 and 20 amino acids designated salusin-alpha and salusin-beta, respectively. It was reported that development of atherosclerosis may be accelerated by salusin-beta and suppressed by salusin-alpha via acyl-CoA cholesterol acyltransferase-1(ACAT-1) regulation in acute coronary syndrome.…”

Protective effect of salusin-α and salusin-β against ethanol-induced gastric ulcer in rats

“…Both are alternative splice products from preprosalusin, the torsion dystonia-related gene (TOR2A) [15]. The presence of preprosalusin in rat stomach tissue is specified in RTq-PCR studies [15,16].…”

“…Both are alternative splice products from preprosalusin, the torsion dystonia-related gene (TOR2A) [15]. The presence of preprosalusin in rat stomach tissue is specified in RTq-PCR studies [15,16]. A previous study reported the detection of salusin-α and salusin-β immunoreactivity in the stomach and in the intestines [17].…”