4 research outputs found
Different Effects of Palmitoyl-L-carnitine and Palmitoyl-CoA on Mitochondrial Function in Rat Ventricular Myocytes
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 the intermediates of FA metabolism, palmitoyl-L-carnitine (Pal-car) and palmitoyl-CoA (Pal-CoA), on mitochondrial function, we measured membrane potential(Δψm), opening of the mitochondrial permeability transition pore (mPTP) and the production of reactive oxygen species (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 5μM) caused a slight hyperpolarization of Δψm (TMRE intensity increased to 115.5 ± 5.4 % and 110.7±1.6 % of the baseline, respectively. p<0.05) but did not open mPTP, 2) a higher concentration of Pal-car (10μM) depolarized Δψm (TMRE intensity decreased to 61.9 ± 12.2 % of the baseline, p<0.01) and opened mPTP (calcein intensity decreased to 70.7 ± 2.8% of the baseline, p<0.01), 3) Pal-CoA depolarized Δψm without opening mPTP, and 4) only the higher concentration of Pal-car (10μM) increased ROS generation (DCF intensity increased to 3.4 ± 0.3 fold of the 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.浜松医科大学学位論文 医博第517号(平成20年10月17日