Year: 2020
Type: dissertation
Abstract: Cyclic GMP (cGMP) is a second messenger that regulate cardiovascular functions and therapies that increase cGMP shows beneficial effects. However, the mechanisms behind some of these effects in the heart are elusive. In the heart, cGMP is synthesized by either soluble guanylyl cyclase (sGC) or natriuretic peptide-dependent activation of GC-A and GC-B. \nThe aim of the thesis was to investigate subcellular cGMP signalling in cardiomyocytes by measuring cGMP using localized FRET biosensors to unravel the signalling pathways involved in myocardial relaxation and apoptosis.\nUsing biosensors, we show that GC-B increases cGMP around the sarcoplasmatic reticulum and troponin I, thus reducing myocardial contractility and accelerating myocardial relaxation. Furthermore, stimulation of both GC-A and GC-B increase cGMP around the outer mitochondrial membrane, and this protects cardiomyocytes from apoptosis. \nSince there are few FRET biosensors available for cGMP, we also developed novel biosensors with high affinity for cGMP, and show their use in several cell types. \nOverall, FRET biosensors are useful tools to reveal organization of signalling pathways and how these mediate functional responses.
Author: Gaia Calamera
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3137836432