Ghrelin role in the regulation of tyrosine hydroxylase, an enzyme involved in hypertension?

NADIA A. LONGO CARBAJOSA; PAULA CORNEJO; FLAVIA M. CERNIELLO; MARIELA M. GIRONACCI; GERARDO CORRADI; MARIO PERELLO

Congreso; III international Congress in translational medicine; 2016

Ghrelin, a hormone produced mainly in stomach upon specific stimuli, is involved in several metabolic and cardiovascular processes. Emerging evidence shows that ghrelin exhibits protective effects on the development of atherosclerosis via multiple pathways, including induction of vasodilation and decrease of angiotensin (AngII)-induced inflammatory factors secretion. In the brain the receptor for ghrelin has been shown to localize in the main cardiovascular control centers in neurons of the nucleus tractus solitarius, and central administration of ghrelin attenuates renal and adipose tissue sympathetic nervous activity. Furthermore, microinjection of ghrelin into the nucleus of the solitary tract, the region of the brain that is important for controlling the autonomic nervous system induced a decrease in the heart rate and mean arterial pressure. Tyrosine hydroxylase (TH), the enzyme that catalyses the first and rate-limiting step in catecholamines biosynthesis, is involved in the development and maintenance of hypertension. The aim of this study was to examine the effect of ghrelin on TH expression and activity. PC12 cells were incubated in the presence or absence of 100 nM ghrelin during different times and TH expression and phosphorylation (as an index of TH activity) were evaluated by Western-blot and immunofluorescence. Our results showed that ghrelin modulate TH expression in PC12 cells in a time-dependent manner. TH expression showed an increase of 29% after 30 min incubation but a decrease of 86% after 24 h incubation in the presence of ghrelin. TH phosphorylation in Ser-40 was increased by 3 and 2 fold above basal in cells treated with ghrelin during 15 and 30 min respectively. In accordance to that observed in PC12 cells, ghrelin induced an increase in PSer40TH expression in the mice medial accumbens shell after ghrelin inyection.Given that TH expression and activity are regulated by the UPS we tested whether proteasome activity could be modulated by ghrelin. A significant increase in proteasome activity was observed after incubation of PC12 cells with ghrelin during 24h. In conclusion, our results suggested that ghrelin may play a role in hypertension by modulting TH activity.