0000000000758363
AUTHOR
Francesca Maiorana
Fibroblast growth factor-21 enhances mitochondrial functions and increases the activity of PGC-1α in human dopaminergic neurons via Sirtuin-1
Abstract Mitochondrial dysfunctions accompany several neurodegenerative disorders and contribute to disease pathogenesis among others in Parkinson’s disease (PD). Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is a major regulator of mitochondrial functions and biogenesis, and was suggested as a therapeutic target in PD. PGC-1α is regulated by both transcriptional and posttranslational events involving also the action of growth factors. Fibroblast growth factor-21 (FGF21) is a regulator of glucose and fatty acid metabolism in the body but little is known about its action in the brain. We show here that FGF21 increased the levels and activity of PGC-1α and elevated mito…
GUANOSINE EFFECTS ON THE MOTOR ACTIVITY OF THE MOUSE STOMACH
Guanine-based purines are part of the purinergic system and recently have been shown to act as neuromodulators, interfering with acetylcholine release by enteric neurons in mouse colon. Due to the pivotal role played by enteric neurons in the control of gastrointestinal motility, the aim of the present study was to verify whether guanosine may affect gastric emptying and the mechanical tone, detected in vitro as changes in intraluminal pressure, of the isolated mouse stomach. Guanosine induced a TTX-insensitive concentration-dependent relaxation of isolated stomach, which at the maximal concentration tested (1 mM), reached about 60% of the relaxation induced by 1 mM isoproterenol. The inhib…
Guanosine negatively modulates the gastric motor function in mouse
The aim of the present study was to evaluate if guanine-based purines may affect the gastric motor function in mouse. Thus, the influence of guanosine on the gastric emptying rate in vivo was determined and its effects on spontaneous gastric mechanical activity, detected as changes of the intraluminal pressure, were analyzed in vitro before and after different treatments. Gastric gavage of guanosine (1.75-10 mg/kg) delayed the gastric emptying. Guanosine (30 μM-1 mM) induced a concentration-dependent relaxation of isolated stomach, which was not affected by the inhibition of the purine nucleoside phosphorylase enzyme by 4'-deaza-1'-aza-2'-deoxy-1'-(9-methylene)-immucillin-H. The inhibitory …
Relaxation Induced By Guanosine in Mouse Stomach
Guanine-based purines are part of the purinergic system and recently have been shown to act as neuromodulators, interfering with acetylcholine release by enteric neurons in mouse colon. Due to the pivotal role played by enteric neurons in the control of gastrointestinal motility, the aim of the present study was to verify whether guanosine may affect gastric emptying and the mechanical tone, detected in vitro as changes in intraluminal pressure, of the isolated mouse stomach. Guanosine induced a TTX-insensitive concentration-dependent relaxation of isolated stomach, which at the maximal concentration tested (1 mM), reached about 60% of the relaxation induced by 1 µM isoproterenol. The inhib…
Fibroblast Growth Factor-21 (FGF-21) enhances mitochondrial functions and increases the activity of PGC-1α in human dopaminergic neurons.
FGF-21 è un fattore di crescita ad azione endocrina principalmente espresso nel fegato con funzioni metaboliche; induce a livello epatico e in altri tessuti incremento di PGC1, ma le sue funzioni a livello cerebrale sono ancora sconosciute. PGC1 è espresso anche nel cervello dove mostra azione neuroprotettiva in neuroni dopaminergici in modelli animali di morbo di Parkinson. Scopo della ricerca era indagare possibili correlazioni tra le due proteine a livello cerebrale. I dati mostrano che FGF-21 induce attivazione di PGC1 mediante la deacetilasi Sirtuina-1 NAD+ dipendente, in neuroni dopaminergici e un incremento dell’attività respiratoria mitocondriale. FGF-21 risulta espresso nel cerv…