ATRIAL NATRIURETIC FACTOR (ANF) ALLEVIATES ENDOPLASMIC RETICULUM STRESS IN RAT ACUTE PANCREATITIS

COURREGES ANA PAULA; BIANCIOTTI LILIANA GRACIELA; VATTA MARCELO SERGIO; NAJENSON ANA CLARA

Mar del Plata

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2016

Sociedad Argentina de Investigación Clínica

The endoplasmic-reticulum (ER) stress response constitutesa cellular process that is triggered by a variety of conditions thatdisturb proteins folding in the E4. EuMaryotic cells have developedan evolutionarily conserved adaptive mechanism, the unfoldedprotein response 724, Yhich aims to clear unfolded proteinsand restore ER homeostasis. Recent studies support that the ERstress is one of the earliest events triggering acute pancreatitisA2. $ased on previous findings from our laboratory shoYing thatA0F significantly attenuates the severity of A2 by reducing trypsinogenactivation and the inflammatory response, Ye sought toestablish Yhether A0F affected E4 stress in a validated A2 animalmodel. A2 Yas induced in Sprague &aYley strain rats g by four repetitive cerulein injections zg/Mg. Thirty minutesbefore the first cerulein injection animals Yere infused Yith eithersaline control or A0F zg/Mg/h for min. FolloYing euthanasiapancreatic samples Yere harvested for Yestern blot analysis andtransmission electronic microscopy TE/ studies. Chaperone$i2, the primary controller of 724, Yas overexpressed in ceruleininduced A2 p , but pretreatment Yith A0F prevented it p ,. 2reliminary results shoY that the proapoptotic transcriptionfactor CH12 Yas also increased in animals Yith A2 and decreasedby A0F. Acinar cells from animals Yith A2 shoYed E4 sYellingas Yell as gap junction disruption, cytoplasm vacuolization, intere intraedema, reduced zymogen granules, nuclear interdigitation,and necrotic areas as revealed by TE/. Animals pretreatedYith A0F shoYed significantly reduced ultraestructural damage,including E4 sYelling. 2resent results shoY that A0F reduced E4sYelling and the major pancreatic ultrastructural features of A2 asYell as 724 response suggesting that the atrial peptide alleviatesE4 stress in early A2 in the rat.