Cardiovascular disease (CVD) is the leading cause of death globally, and tissue ischemia induces disorders including myocardial infarction, pulmonary arterial hypertension, and atherosclerosis. Ischemic conditions considerably alter cellular homeostasis as well as metabolism and can result in cardiovascular dysfunction. Therefore, there is a dire need to develop a novel treatment strategy for curing myocardial ischemia via manipulating cellular networking and metabolism. Furthermore, studies have shown that ischemic conditions induce cellular stress such that it modifies the expression of various cellular proteins and may even promote cell death.
Cellular proteins must fold into a three-dimensional, native state to become functional. To ensure efficient folding and prevent aggregation, molecular chaperones assist with the folding/refolding process. Additionally, chaperones regulate cellular proteostasis through the ubiquitin-proteosome system (UPS) or autophagy. The heat-shock protein (HSP) is a molecular chaperone family upregulated during stress conditions to assist cells with proper protein folding, stability, and turnover. Specifically, the 70-kDa heat-shock protein (Hsp70) has numerous cytoprotective and immunomodulatory effects through its interaction with components of several cellular pathways. This interaction is dependent on nucleotide exchange factors (NEFs) to hold the open conformation of HSP70's nucleotide-binding domain (NBD). Proteins in the Bcl-2- associated athanogene (BAG) family are a group of co-chaperones that interact with the ATPase domain of HSP70 and help maintain homeostasis. The BAG family proteins (BAG1-6) share an evolutionarily conserved region at their C-termini (the BAG domain), and BAG5 specifically is unique in that it contains five of these domains. BAG5 plays a crucial role in maintaining cellular homeostasis and viability. This project explores the role of BAG5 as a co-chaperone and potential therapeutic tool to improve cardiomyocyte function under ischemic conditions.
Bachelor of Science (B.S.)
College of Medicine
Burnett School of Biomedical Sciences
Length of Campus-only Access
Mukker, Avni, "Role of BAG5 in Maintaining Cellular Proteostasis During Stress Conditions" (2022). Honors Undergraduate Theses. 1320.