| 1. |
- Ponsot, Elodie, 1973-, et al.
(författare)
-
Mitochondrial tissue specificity of substrates utilization in rat cardiac and skeletal muscles
- 2005
-
Ingår i: Journal of Cellular Physiology. - Hoboken, USA : John Wiley & Sons. - 0021-9541 .- 1097-4652. ; 203:3, s. 479-86
-
Tidskriftsartikel (refereegranskat)abstract
- As energetic metabolism is crucial for muscles, they develop different adaptations to respond to fluctuating demand among muscle types. Whereas quantitative characteristics are known, no study described simultaneously quantitative and qualitative differences among muscle types in terms of substrates utilization patterns. This study thus defined the pattern of substrates preferential utilization by mitochondria from glycolytic gastrocnemius (GAS) and oxidative soleus (SOL) skeletal muscles and from heart left ventrical (LV) in rats. We measured in situ, ADP (2 mM)-stimulated, mitochondrial respiration rates from skinned fibers in presence of increasing concentrations of pyruvate (Pyr) + malate (Mal), palmitoyl-carnitine (Palm-C) + Mal, glutamate (Glut) + Mal, glycerol-3-phosphate (G3-P), lactate (Lact) + Mal. Because the fibers oxygen uptake (Vs) followed Michaelis-Menten kinetics in function of substrates level we determined the Vs and Km, representing maximal oxidative capacity and the mitochondrial sensibility for each substrate, respectively. Vs were in the order GAS < SOL < LV for Pyr, Glu, and Palm-C substrates, whereas in the order SOL = LV < GAS with G3-P. Moreover, the relative capacity to oxidize Palm-C is extremely higher in LV than in SOL. Vs was not stimulated by the Lact substrate. The Km was equal for Pyr among muscles, but much lower for G3-P in GAS and lower for Palm-C in LV. These results demonstrate qualitative mitochondrial tissue specificity for metabolic pathways. Mitochondria of glycolytic muscle fibers are well adapted to play a central role for maintaining a satisfactory cytosolic redox state in these fibers, whereas mitochondria of LV developed important capacities to use fatty acids.
|
|
| 2. |
- Zoll, J, et al.
(författare)
-
Acute myocardial ischaemia induces specific alterations of ventricular mitochondrial function in experimental pigs
- 2005
-
Ingår i: Acta Physiologica Scandinavica. - Oxon, United Kingdom : Blackwell Publishing. - 0001-6772 .- 1365-201X. ; 185:1, s. 25-32
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: As cardiac metabolic flexibility is crucial, this study examined whether acute ischaemia can induce specific qualitative alterations of the mitochondrial metabolic pathways as well as energy transfer systems.Methods: Left descending coronary artery ligation was performed after sternotomy in eight pigs and the heart was excised after 45 min of ischaemia. Maximal O2 uptake (V(max), micromol O2 min(-1) g(-1) dry weight) of saponin-skinned myofibres were measured from ischaemic and non-ischaemic area of ventricular myocardium.Results: V(max) decreased by approximately 20% in ischaemic myocardium with both glutamate-malate (18.1 +/- 1.3 vs. 22.1 +/- 1.7 in control, P < 0.05) and pyruvate substrates (19.3 +/- 1.0 vs. 23.3 +/- 2.0 in control, P < 0.05) whereas no difference was observed with palmitoyl carnitine (15.6 +/- 1.8 vs. 16.6 +/- 0.9 in control). The K(m) of mitochondrial respiration for ADP decreased in ischaemic heart by 24% (679 +/- 79 vs. 899 +/- 84 microm of ADP in control, P < 0.05). Moreover, the mitochondrial creatine kinase efficacy (K(m) without creatine/K(m) with creatine), representative of the coupling of oxidative phosphorylation process with the mitochondrial creatine kinase, was reduced in ischaemic heart (11.6 +/- 2.5 in ischaemic vs. 18.0 +/- 2.2 in control, P < 0.05).Conclusions: These findings argue for specific mitochondrial impairments at the level of pyruvate oxidation and creatine kinase channelling system after an acute period of in vivo ischaemia, whereas the lipid mitochondrial oxidation pathway seems to be preserved. Such a loss of metabolic flexibility following acute ischaemia could become an early feature of metabolic dysregulation of the heart.
|
|
