Date of Award
2010
Degree Type
Thesis
Degree Name
Master of Science
Program
Pharmacology and Toxicology
Supervisor
Dr. Peter Chidiac
Second Advisor
Dr. Qingping Feng
Third Advisor
Dr. Robert Gros
Abstract
Chronic stimulation of cardiac G protein-coupled receptors, particularly through Gq∕ll and Gs signalling pathways, promotes cardiomyocyte hypertrophy and plays a pivotal role in heart failure development. RGS2 is unique in its selectivity for attenuating Gq signals and has emerged as an important negative regulator of cardiac hypertrophy. We investigated the potential role of RGS2 in modulating the hypertrophie effects of the β- AR agonist isoproterenol (ISO) in cardiomyocytes. Furthermore, our lab discovered a novel RGS2 interaction with the initiation factor eIF2B, which catalyzes a rate-limiting step in mRNA translation. This interaction impedes eIF2B function, leading to inhibition of de novo protein synthesis, a requisite component of cardiac hypertrophy. We investigated whether this interaction may serve as an additional mechanism in the anti- hypertrophic effects of RGS2. Our results indicate that RGS2 can impede both β-AR- induced hypertrophy and protein synthesis in cardiomyocytes, establishing its role as a multifaceted regulator of cardiac hypertrophy.
Recommended Citation
Sobiesiak, Alina J., "MECHANISM OF THE PROTECTIVE EFFECT OF REGULATOR OF G PROTEIN SIGNALLING (RGS) PROTEIN 2 IN CARDIOMYOCYTE HYPERTROPHY" (2010). Digitized Theses. 4655.
https://ir.lib.uwo.ca/digitizedtheses/4655