HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 295/1/H105    most recent 01307.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Tominaga, H. Articles by Hayashi, H. PubMed PubMed Citation Articles by Tominaga, H. Articles by Hayashi, H.

Different effects of palmitoyl-L-carnitine and palmitoyl-CoA on mitochondrial function in rat ventricular myocytes

Internal Medicine III, Hamamatsu University School of Medicine, Hamamatsu, Japan

Submitted 7 November 2007 ; accepted in final form 4 May 2008

Although mitochondrial oxidative catabolism of fatty acid (FA) is a major energy source for the adult mammalian heart, cardiac lipotoxity resulting from elevated serum FA and enhanced FA use has been implicated in the pathogenesis of heart failure. To investigate the effects of intermediates of FA metabolism [palmitoyl-L-carnitine (Pal-car) and palmitoyl-CoA (Pal-CoA)] on mitochondrial function, we measured membrane potential (_m), opening of the mitochondrial permeability transition pore (mPTP), and the production of ROS in saponin-treated rat ventricular myocytes with a laser scanning confocal microscope. Our results revealed that 1) lower concentrations of Pal-car (1 and 5 µM) caused a slight hyperpolarization of _m [tetramethylrhodamine ethyl ester (TMRE) intensity increased to 115.5 ± 5.4% and 110.7 ± 1.6% of baseline, respectively, P < 0.05] but did not open the mPTP, 2) a higher concentration of Pal-car (10 µM) depolarized _m (TMRE intensity decreased to 61.9 ± 12.2% of baseline, P < 0.01) and opened the mPTP (calcein intensity decreased to 70.7 ± 2.8% of baseline, P < 0.01), 3) Pal-CoA depolarized _m without opening the mPTP, and 4) only the higher concentration of Pal-car (10 µM) increased ROS generation (2',7'-dichlorofluorescein diacetate intensity increased to 3.4 ± 0.3-fold of baseline). We concluded that excessive exogenous intermediates of long-chain saturated FA may disturb mitochondrial function in different ways between Pal-car and Pal-CoA. The distinct mechanisms of the deteriorating effects of long-chain FA on mitochondrial function are important for our understanding of the development of cardiac diseases in systemic metabolic disorders.

mitochondrial membrane potential; mitochondrial permeability transition pore; reactive oxygen species production