Skip Navigation


Cardiovascular Research Advance Access first published online on February 11, 2008
This version [Corrected Proof] published online on February 22, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn030
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
78/3/533    most recent
cvn030v3
cvn030v2
cvn030v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Fang, K.-M.
Right arrow Articles by Wu, M.-L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fang, K.-M.
Right arrow Articles by Wu, M.-L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Free fatty acids act as endogenous ionophores, resulting in Na+ and Ca2+ influx and myocyte apoptosis

Kwang-Ming Fang1,2, An-Sheng Lee3, Ming-Jai Su3, Chien-Liang Lin1, Chung-Liang Chien4,* and Mei-Lin Wu1,*

1 Institutes of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan
2 Dept. of Dental Laboratory Technology, Central Taiwan University of Science and Technology, Taichung, Taiwan
3 Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan
4 Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan

* Correspondence Drs. Mei-Lin Wu and Chung-Liang Chien Institutes of Physiology and Anatomy and Cell Biology College of Medicine National Taiwan University No. 1, Section 1, Jen-Ai Road, Taipei, Taiwan Fax: +886-2-23224330 Tel: +886-2-23123456 ext 8242 E-mail: meilin{at}ntu.edu.tw

Aim: Disturbances in lipid metabolism have been suggested to play an important role in myocardial damage. Marked accumulation of free fatty acids (FFAs), including arachidonic acid (AA), palmitic acid, oleic acid, and linoleic acid, occurs during post-ischemia and reperfusion (post-I/R). Possible cellular mechanism of AA/FFAs-induced mycoyte apoptosis was investigated.

Methods and Results: In neonatal rat ventricular myocytes, AA/FFAs activate a novel non-selective cation conductance (NSCC), resulting in both intracellular Ca2+ and Na+ overload. AA caused sustained cytosolic [Na+]cyt and [Ca2+]cyt overload, resulting in mitochondrial [Na+]m and [Ca2+]m overload, which induced caspase-3-mediated apoptosis. Similar apoptotic effects were seen using Na+-ionophore cocktail/Ca2+-free medium, which induced [Na+]cyt and [Na+]m, but not [Ca2+]cyt and [Ca2+]m overload. Electron microscopy showed that inhibition of [Na+]m overload prevented disruption of the mitochondrial membrane, showing that [Na+]m overload is an important upstream signal in AA- and FFAs-induced myocyte apoptosis.

Conclusions: AA and FFAs, which accumulate in the myocardium during post-I/R, may therefore act as naturally occurring endogenous ionophores and contribute to the myocyte death seen during post-I/R.

KEYWORDS arachidonic acid; mitochondrial Na+; apoptosis

Time for primary review: 30 days

The first two authors have equal contributions to this work.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.