| Title: |
DEFICIENCY OF ATAXIA-TELANGIECTASIA MUTATED KINASE AFFECTS AUTOPHAGY AFTER MYOCARDIAL INFARCTION |
| Authors: |
Crawford, Claire C.; Thrasher, Patsy R.; Scofield, Dr. Stephanie L.C.; Dalal, Dr. Suman; Singh, Dr. Mahipal; Singh, Dr. Krishna |
| Source: |
Appalachian Student Research Forum [2018-2024] |
| Publisher Information: |
Digital Commons @ East Tennessee State University |
| Publication Year: |
2018 |
| Collection: |
Digital Commons @ East Tennessee State University |
| Subject Terms: |
ATM; Autophagy; Myocardial Infarction; Biology |
| Description: |
Background: Autophagy is a conserved physiological process in the body that functions to maintain homeostasis via degradation and recycling of dysfunctional proteins and even entire organelles. It is typically triggered by nutritional stress and/or growth factor deprivation and ultimately results in the packaging of cellular components into autophagosomes. These autophagosomes then fuse with lysosomes to be degraded. Autophagy is suggested to play a significant role in cardiac remodeling, particularly following myocardial infarction (MI). Ataxia-telangiectasia mutated kinase (ATM) is a cell cycle checkpoint protein activated in response to DNA damage. Mutations in ATM cause a multi-systemic disease known as Ataxia-telangiectasia (AT). The present study aims to investigate the relationship between ATM and autophagy in the heart, particularly post-MI. Methods: Wild-type (WT) and ATM heterozygous (hKO; aged ~4 months) were injected with either bafilomycin (Baf; autophagy inhibitor) or rapamycin (Rap; autophagy activator) for 30 minutes. MI was then induced mice by ligation of the left anterior descending coronary artery. Heart function was measured using M-mode echocardiography 4 hours post-MI. For cellular analysis of autophagy, confluent cultures of cardiac fibroblasts were isolated from adult male rats and treated with KU-55933 (KU; specific ATM inhibitor) in serum-free media for 4 hours. Cardiac fibroblasts were also isolated from ATM WT, heterozygous (hKO), and knockout (KO) mice, grown to confluency, and serum-starved for 4 hours. Levels of microtubule-associated protein light chain 3-II (LC3-II), a marker for autophagy, was examined in the heart and cell lysates using western blots. Results: M-mode echocardiography revealed that MI decreases heart function in both genotypes as measured by decreased %FS and EF. No change in heart function was observed between WT-MI and hKO-MI groups following Baf treatment. Rap treatment resulted in the functional recovery of the heart in WT-MI, not in hKO-MI group. Levels of ... |
| Document Type: |
text |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
https://dc.etsu.edu/asrf/2018/schedule/148 |
| Availability: |
https://dc.etsu.edu/asrf/2018/schedule/148 |
| Accession Number: |
edsbas.9583701C |
| Database: |
BASE |