Amylin prevents TRAIL-mediated apoptotic effects of reserpine in the rat gastric mucosa.
We have previously shown that amylin has a protective effect upon the damaged rat gastric mucosa via a cytokine-mediated mechanism. Here, the effects of amylin on the proapoptotic cytokine TNF-related-apoptosis-inducing-ligand (TRAIL) were tested in the rat gastric mucosa damaged by reserpine administration in vivo. Intraperitoneal administration of reserpine in adult male Sprague-Dawley rats resulted in increased TRAIL expression in the gastric mucosa. Immunohistochemistry showed that the TRAIL death-receptor 5 (DR5) was constitutively expressed by the mucosa cells. Western blot showed that pretreatment of reserpine-treated rats with amylin was associated with attenuated expression of TRAIL. In the same samples, we also investigated about TRAIL-related signaling and observed that activation of caspases-8 and -3 occurs in parallel to increased TRAIL expression in rats treated with reserpine. Similarly to the latter, activation of caspases was attenuated in rats pretreated with amylin. Treatment with reserpine was associated with increased expression of the proapoptotic protein Bax, whereas that of the antiapoptotic protein Bcl-2 was significantly decreased. Amylin prevented the effects of reserpine on these genes. Reserpine sets into motion mechanisms of apoptosis in the rat gastric mucosa, which appear mediated, at least in part, by TRAIL. In addition, TRAIL downstream signaling is activated along with subversion of gene expression related to apoptosis. Amylin was able to prevent detrimental effects of reserpine. Finally, amylin and related molecules may be envisioned as protective agent in gastric mucosa damage.
Cantarella
Giuseppina
G
Department of Experimental and Clinical Pharmacology, University of Catania School of Medicine, Viale Andrea Doria, 6, 95125 Catania, Italy.
Di Benedetto
Giulia
G
Martinez
Giuseppa
G
Loreto
Carla
C
Clementi
Giuseppe
G
Cantarella
Antonio
A
Prato
Agatina
A
Bernardini
Renato
R
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D005753:Gastric Mucosa / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D058228:Islet Amyloid Polypeptide; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D018759:Adrenergic Uptake Inhibitors; D000682:Amyloid; D000897:Anti-Ulcer Agents; D058228:Islet Amyloid Polypeptide; D019253:Proto-Oncogene Proteins c-bcl-2; D053221:TNF-Related Apoptosis-Inducing Ligand; D051028:bcl-2-Associated X Protein; D012110:Reserpine