| Title: |
Deficiency of Ataxia‐telangiectasia Mutated Kinase Induces Autophagic Impairment Following Myocardial Infarction |
| Authors: |
Thrasher, Patsy R.; Scofield, Stephanie L.C.; Dalal, Suman; Singh, Mahipal; Singh, Krishna |
| Contributors: |
U.S. Department of Veterans Affairs; National Institutes of Health; National Heart, Lung, and Blood Institute |
| Source: |
The FASEB Journal ; volume 31, issue S1 ; ISSN 0892-6638 1530-6860 |
| Publisher Information: |
Wiley |
| Publication Year: |
2017 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
Autophagy, a conserved physiological process, 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 to lysosomes to be degraded. Although often associated with nutrient deprivation, autophagy is suggested to play a significant role in cardiac remodeling, particularly following myocardial infarction (MI). Ataxia‐telangiectasia mutated kinase (ATM) is a 370 kDa threonine/serine kinase. Mutations in ATM cause a multisystemic disease known as Ataxia‐telangiectasia (AT). Although the role of ATM in cell cycle progression is well known, its role in autophagy is not yet completely understood. The present study tested the hypothesis that deficiency of ATM impairs autophagic response in the heart post‐MI. MI was induced in ~4 month old wild‐type (WT) and ATM heterozygous knockout (hKO) mice by ligation of the left anterior descending artery. The mice were sacrificed 4 hours following MI. Levels of microtubule‐associated protein light chain 3 (LC3), sequestosome 1 (p62), cathepsin D, and phosphorylation of Akt and glycogen synthase kinase 3β (GSK3‐β) were analyzed in the heart lysates using western blots. Ratio of LC3II/LC3I, marker of autophagy induction and autophagosome formation, was significantly lower in hKO‐sham when compared to WT‐sham group (P |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1096/fasebj.31.1_supplement.846.14 |
| Availability: |
http://dx.doi.org/10.1096/fasebj.31.1_supplement.846.14 |
| Rights: |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
| Accession Number: |
edsbas.9E73DE47 |
| Database: |
BASE |