<p dir="ltr">Phospholipase C (PLC) enzymes are essential for normal cardiovascular function. These enzymes hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP<sub>2</sub>) at the inner leaflet of the plasma membrane, producing diacylglycerol (DAG) and inositol phosphates (IP<sub>3</sub>). IP<sub>3</sub> increases intracellular Ca<sup>2+</sup>, a key secondary messenger in cardiovascular activity. Changes in PLC expression and activity, specifically PLCβ3, have been found to play a critical role in cardiac hypertrophy and contractility. Cardiac hypertrophy, especially left ventricular hypertrophy, is a primary cause of ischemic heart disease, the leading cause of mortality worldwide. Despite the importance of these enzymes, a selective inhibitor for studying their function in cells and animal models has not yet been discovered. To address this unmet need, a lentiviral system for expressing human PLCβ3 and its two major activators, the heterotrimeric G protein subunits Ga<sub>q</sub> and Gβγ was developed. These constructs were then utilized to establish a high-throughput screening methodology with the aim of identifying a novel allosteric inhibitor of PLCβ3, and ultimately other PLCs.</p>
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/25705338 |
| Date | 28 April 2024 |
| Creators | Tasneem Jamila Ikram (18452550) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/thesis/_b_Searching_For_Inhibitors_of_PLC_3_A_High-Throughput_Approach_b_/25705338 |
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