Učinak gvanilinskih peptida na signalni sustav bradikinina u kulturi HEK293 stanica

master's thesis

• Title (english): Effects of guanylin peptides on bradykinin signaling pathway in HEK293 cell culture
• Author: Karolina Rabik
• Mentor: Aleksandra Dugandžić (mentor)
• Mentor: Zoran Tadić (mentor)
• Committee member: Zoran Tadić (predsjednik povjerenstva)
• Committee member: Aleksandra Dugandžić (član povjerenstva)
• Committee member: Inga Marijanović (član povjerenstva)
• Committee member: Mirjana Kalafatić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2013-12-06, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Okluzija cerebralne arterije dovodi do moždanog udara te posljedično moždanog edema koji pridonosi povećanju ishemijske ozljede. U ovom radu istraživati će se djelovanje gvanilinskih peptida, gvanilina i urogvanilina, agonista gvanilat ciklaze C, na signalni sustav bradikinina kao glavnog uzročnika nastanka moždanog edema nakon moždanog udara. Cilj je razjasniti mehanizam djelovanja gvanilinskih peptida na stanicama HEK293 te njihovo djelovanje na bradikinin, kao što smo nedavno prikazali za agoniste gvanilat ciklaze A, atrijski natriuretski peptid (ANP) i urodilatin. U ovom radu sam koristila metodu priklještenih potencijala (slow whole cell patch-clamp) za mjerenje membranskih potencijala HEK293 stanica, kojom smo pokazali da gvanilin i urogvanilin kao i njihov sekundarni glasnik, ciklički GMP, depolariziraju staničnu membranu i inhibiraju djelovanje bradikininskog signalnog puta preko aktivacije RGS proteina.Rezultati ovog istraživanja pretpostavljaju moguću zaštitnu ulogu gvanilinskih peptida u smanjenju moždanog edema te posljedično smanjenja veličine ishemijske ozljede mozga.

Abstract (english)

The occlusion of cerebral arteries leads to a stroke and consequently to a cerebral edema, which contributes to an increase of ischemic injury. In this study we investigate the effect of guanylin peptides, guanylin and uroguanylin and guanylate cyclase C agonist on the signaling system of bradykinin, which is the main contributor to the occurrence of cerebral edema after the stroke. The aim of this study is to clarify the activity mechanism of the guanylin peptides on HEK293 cells and their effect on bradykinin, as we have recently shown on the example of guanylate cyclase agonist A, atrial natriuretic peptide (ANP) and urodilatin. In this experiment we used slow-whole cell patch-clamp technique to measure a membrane potential in HEK293 cells. We showed that guanylin and uroguanylin, just like their secondary messenger cyclic GMP, depolarize a plasma membrane and they inhibit the activity of bradykinin signaling pathway via an activation of RGS protein. Results of this study suggest a possible protective role of guanylin peptides in a decrease of cerebral edema and also a decrease of an ischemic brain injury.

• Keywords: natriuretski peptidi; gvanilin; urogvanilin; patch-clamp
• Keywords (english): natriuretic peptides; guanylin; uroguanylin; patch-clamp
• Language: croatian
• URN:NBN: urn:nbn:hr:217:058889
• Study programme: Title: Experimental Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra eksperimentalne biologije (magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2017-04-27 12:46:35