EXTRACELLULAR PROTEOLYSIS OF THE HORMONE GHRELIN GENERATES A SPECIFIC SUBSET OF GHRELIN-DERIVED PEPTIDES WITH DIFFERENTIAL BIOACTIVITIES

FITTIPALDI, ANTONELA; LUFRANO, DANIELA; FERNÁNDEZ, GIMENA; CASTROGIOVANNI, DANIEL; DE FRANCESCO, PABLO NICOLÁS; LUYT, LEONARD G.; TREJO, SEBASTIAN; PERELLO, MARIO

Mar del Plata

Congreso; SAIC SAFE SAB SAP 2019; 2019

Sociedad Argentina de Investigación Clínica

The stomach-derived hormone ghrelin is a peptide of 28residues acylated with an octanoic acid at Ser3. TheN-terminal sequence of ghrelin along with the octanoyl group are essential toact on the ghrelin receptor. Here, we tested the hypothesis that ghrelin can beextracellularly cleaved in order to generate ghrelin-derived peptides withdifferential bioactivities. Initially, we incubated ghrelin with plasma andthen performed MALDI-TOF MS analysis. We found that ghrelin is mainly cleaved inthe region extended from residue 11 to 16. Then, we incubated ghrelin with livercarcinoma HepG2 cells or with extracellular medium derived from these cells,and also found that ghrelin cleavage occurs in the same ?hot cleavage region?of its sequence. Since ghrelin1-14 was derived from ghrelin proteolysis, wethen tested the ability of this shorter version of ghrelin to act in the brainand stimulate appetite in mice. We found that ghrelin increases food intake (0.29g vs. 0.07 g in vehicle-injected mice, p-value 0.0008) while ghrelin1-14 failedto do it (0.005 g).