| Parkin protein deficiency exacerbates cardiac injury and reduces survival following myocardial infarction. | |
| | |
MedLine Citation:
|
PMID: 23152496 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
It is known that loss-of-function mutations in the gene encoding Parkin lead to development of Parkinson disease. Recently, Parkin was found to play an important role in the removal of dysfunctional mitochondria via autophagy in neurons. Although Parkin is expressed in the heart, its functional role in this tissue is largely unexplored. In this study, we have investigated the role of Parkin in the myocardium under normal physiological conditions and in response to myocardial infarction. We found that Parkin-deficient (Parkin(-/-)) mice had normal cardiac function for up to 12 months of age as determined by echocardiographic analysis. Although ultrastructural analysis revealed that Parkin-deficient hearts had disorganized mitochondrial networks and significantly smaller mitochondria, mitochondrial function was unaffected. However, Parkin(-/-) mice were much more sensitive to myocardial infarction when compared with wild type mice. Parkin(-/-) mice had reduced survival and developed larger infarcts when compared with wild type mice after the infarction. Interestingly, Parkin protein levels and mitochondrial autophagy (mitophagy) were rapidly increased in the border zone of the infarct in wild type mice. In contrast, Parkin(-/-) myocytes had reduced mitophagy and accumulated swollen, dysfunctional mitochondria after the infarction. Overexpression of Parkin in isolated cardiac myocytes also protected against hypoxia-mediated cell death, whereas nonfunctional Parkinson disease-associated mutants ParkinR42P and ParkinG430D had no effect. Our results suggest that Parkin plays a critical role in adapting to stress in the myocardium by promoting removal of damaged mitochondria. |
| | |
Authors:
|
Dieter A Kubli; Xiaoxue Zhang; Youngil Lee; Rita A Hanna; Melissa N Quinsay; Christine K Nguyen; Rebecca Jimenez; Susanna Petrosyan; Anne N Murphy; Asa B Gustafsson |
Related Documents
:
|
22965286 - Left ventricular noncompaction in patients with β-thalassemia: uncovering a previously... 23679996 - Changes in vagal reactivity to the sympathicotonia during the progression of heart fail... 20485236 - Short and long-term outcomes of percutaneous revascularization in patients with prior c... 20877686 - Percutaneous coronary intervention vs coronary artery bypass grafting in the management... 12830046 - Late recovery of atrioventricular conduction after pacemaker implantation for complete ... 2704246 - Screening of positive inotropic agents in isolated cardiac preparations from different ... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-11-14 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: 288 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2013 Jan |
Date Detail:
|
Created Date: 2013-01-14 Completed Date: 2013-03-26 Revised Date: 2013-04-16 |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
|
Languages: eng Pagination: 915-26 Citation Subset: IM |
Affiliation:
|
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093-0758, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Blotting, Western Electrocardiography Male Mice Mice, Knockout Microscopy, Electron, Transmission Microscopy, Fluorescence Mitochondria, Heart / physiology Myocardial Infarction / physiopathology* Rats, Sprague-Dawley Survival* Ubiquitin-Protein Ligases / genetics, physiology* |
| Grant Support | |
ID/Acronym/Agency:
|
R01HL087023/HL/NHLBI NIH HHS; R01HL101217/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
EC 6.3.2.19/Ubiquitin-Protein Ligases; EC 6.3.2.19/parkin protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Matrix rigidity activates Wnt signaling through down-regulation of Dickkopf-1 protein.
Next Document: Histone demethylase KDM6B promotes epithelial-mesenchymal transition.