Mitochondria provide the main energy required for cardiac excitation-contraction coupling via aerobic oxidative phosphorylation (OXPHOS) process. Accumulation of reactive oxygen species (ROS), by-products of mitochondrial respiration, within dysfunctional mitochondria results in the activation of cardiac cell death pathways and has been associated with heart failure development. Therefore, maintaining mitochondrial homeostasis as a balance between mitochondrial biogenesis and degradation is of great importance toward cardiac proper functioning. In addition to the importance of mitochondrial energy supply, gap junctions, intercellular channels which connect plasma membrane of adjacent cardiomyocytes, by propagating action potential throughout the myocardium maintain cardiac synchronous beating and rhythm. Gap junctions have a rapid turnover and impair of gap junction quality control impacts cell-to-cell communication; resulting in electrical conduction abnormalities and arrhythmogenesis. Therefore, understanding the underlying mechanism the quality control of mitochondria and gap junctions profoundly contributes toward understating the genesis of cardiomyopathy. Furthermore, cardiovascular problems in HIV (Human immunodeficiency virus) positive patients whose viral load is controlled via antiretroviral therapy remains a problem while the underlying mechanism remains elusive. The current study has used an in vitro model of primary neonatal rat ventricular cardiomyocytes (NRVCs) to discover the molecular mechanisms of mitochondrial as well as gap junction quality control under normal and stress conditions. Furthermore, electrical activities of the primary cardiomyocytes were recorded using microelectrode array (MEA) system and important electrophysiological components such as impulse propagation pattern and conduction velocity were extracted from the complex signal recordings. Overall, we have pursued four main aims; Aim 1. Dysregulation of mitochondrial quality control machinery leads to cardiac death; Aim 2. HIV-1 Tat (transcriptional transactivator) dysregulates cardiac homeostasis via mitochondrial pathway; Aim 3. Impairment of protein quality control impacts the quality of gap junction; Aim 4. Inhibition of gap junction quality dysregulates electrical signal propagation within the culture. / Bioengineering
| Identifer | oai:union.ndltd.org:TEMPLE/oai:scholarshare.temple.edu:20.500.12613/1292 |
| Date | January 2018 |
| Creators | Ghasemi Tahrir, Farzaneh |
| Contributors | Khalili, Kamel, 1951-, Lelkes, Peter I., Marcinkiewicz, Cezary, Bellas, Evangelia, Sariyer, Ilker K. |
| Publisher | Temple University. Libraries |
| Source Sets | Temple University |
| Language | English |
| Detected Language | English |
| Type | Thesis/Dissertation, Text |
| Format | 169 pages |
| Rights | IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available., http://rightsstatements.org/vocab/InC/1.0/ |
| Relation | http://dx.doi.org/10.34944/dspace/1274, Theses and Dissertations |
Page generated in 0.0025 seconds