Reversible ischemic inhibition of F1F0-ATPase in rat and human myocardium

Ylitalo, Kari; Ala-Rämi, Antti; Vuorinen, Klaus; Peuhkurinen, Keijo; Lepojärvi, Martti; Kaukoranta, Päivi; Kiviluoma, Kai; Hassinen, Ilmo E.

doi:10.1016/s0005-2728(00)00261-9

Cited by 39 publications

(27 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As it was previously demonstrated by several authors (Corbucci, 2000;Ylitalo et al, 2001;Marin-Garcia and Goldenthal, 2002), our results clearly show that oxidative phosphorylation is very sensitive to ischemia, which dramatically affects mitochondrial respiratory chain (Fig. 1), as it can be shown by the decrease in the respiratory control ratio [that is, the ratio between the oxygen consumption during active phosphorylation (state 3) and after active phosphorylation (state 4)], when compared to the value obtained in mitochondria from the control group (2.71 T 0.42 versus 1.51 T 0.13; P = 0.0002).…”

Section: Resultssupporting

confidence: 73%

Valsartan improves mitochondrial function in hearts submitted to acute ischemia

Monteiro

Duarte

Gonçalves

et al. 2005

European Journal of Pharmacology

View full text Add to dashboard Cite

The effect of valsartan, an angiotensin II-type I receptor blocker, on the mitochondrial function, was studied using an ex vivo animal model (hearts from Wistar rats), perfused in a Langendorff system and then submitted to global acute ischemia. Parameters evaluated were: membrane electrical potential (DW, using a tetraphenylphosphonium-TPP + -electrode), oxygen consumption by the respiratory chain (Clark-type O 2 electrode), phosphorylation lag phase (time necessary to phosphorylate a fixed amount of ADP) and ATP / ADP ratio (adenine nucleotides quantified by high-pressure liquid chromatography-HPLC). Valsartan acts preferentially in the phosphorylation, increasing ATP / ADP ratios (succinate: 1.6 T 0.4 versus 0.5 T 0.1-P < 0.05; ascorbate/N,N,N V,N V-tetramethyl-P-phenylenodiamine-TMPD: 1.1 T 0.2 versus 0.4 T 0.1-p < 0.05 versus ischemia in the absence of valsartan) and decreasing lag phase (glutamate/malate: 50.0 T 9.6 s versus 127.2 T 19.03 s -84.6 T 16.2% versus 215.3 T 32.2%; P = 0.01; succinate: 111.8 T 33.1 s versus 275.73 T 45.99 s -168.2 T 49.8% versus 414.9 T 69.2%; P = 0.02 or ascorbate/TMPD: 11.0 T 3.9 s versus 62.4 T 11.63 s -34.9 T 12.4% versus 198.1 T 36.9%; P = 0.001 versus ischemia in the absence of valsartan). This enables a higher energy production in hearts submitted to acute ischemia, for which having energy becomes critical to preserve mitochondrial function. These mechanisms allow us to better understand valsartan cytoprotection in ischemic cardiomyopathy. D

show abstract

Section: Resultssupporting

confidence: 73%

Valsartan improves mitochondrial function in hearts submitted to acute ischemia

Monteiro

Duarte

Gonçalves

et al. 2005

European Journal of Pharmacology

View full text Add to dashboard Cite

show abstract

“…Oligomycin, a potent inhibitor of mitochondrial F 1 F 0 -ATPase, has long been used to inhibit state 3 respiration in isolated mitochondria (27). However, recent observations by Ylitalo et al (28) showed that the concentration of oligomycin required for 50% inhibition of the mitochondrial F 1 F 0 -ATPase was fivefold lower than its concentration required for 50% inhibition of electron flux through the respiratory chain, and hence, oxygen consumption. This leaves open a window of oligomycin concentrations at which intracellular AMP is elevated while simultaneously oxygen consumption is not inhibited.…”

Section: Resultsmentioning

confidence: 92%

“…The drop in intracellular ATP acts synergistically, because the AMP-driven activation is inhibited by high ATP, making the AMP/ATP ratio the major determinant of AMP kinase activation (27,28). However, this study requires the inhibition of mitochondrial ATP production, while at the same time aerobic metabolism is not inhibited.…”

Section: Resultsmentioning

confidence: 98%

Contraction-Induced Fatty Acid Translocase/CD36 Translocation in Rat Cardiac Myocytes Is Mediated Through AMP-Activated Protein Kinase Signaling

Luiken

Coort²,

Willems³

et al. 2003

Diabetes

265

264

View full text Add to dashboard Cite

Contraction of rat cardiac myocytes induces translocation of fatty acid translocase (FAT)/CD36 and GLUT4 from intracellular stores to the sarcolemma, leading to enhanced rates of long-chain fatty acid (FA) and glucose uptake, respectively. Because intracellular AMP/ ATP is elevated in contracting cardiac myocytes, we investigated whether activation of AMP-activated protein kinase (AMP kinase) is involved in contractioninducible FAT/CD36 translocation. The cell-permeable adenosine analog 5-aminoimidazole-4-carboxamide-1-␤-D-ribofuranoside (AICAR) and the mitochondrial inhibitor oligomycin, similar to 4-Hz electrostimulation, evoked a more than threefold activation of cardiomyocytic AMP kinase. Both AICAR and oligomycin stimulated FA uptake into noncontracting myocytes by 1.4-and 2.0-fold, respectively, but were ineffective in 4 Hz-contracting myocytes. These findings indicate that both agents stimulate FA uptake by a similar mechanism as electrostimulation, involving activation of AMP kinase, as evidenced from phosphorylation of acetyl-CoA carboxylase. Furthermore, the stimulating effects of both AICAR and oligomycin were antagonized by blocking FAT/CD36 with sulfo-N-succinimidylpalmitate, but not by inhibiting phosphatidylinositol 3-kinase with wortmannin, indicating the involvement of FAT/CD36, but excluding a role for insulin signaling. Subcellular fractionation showed that oligomycin was able to mobilize intracellularly stored FAT/CD36 to the sarcolemma. We conclude that AMP kinase regulates cardiac FA use through mobilization of FAT/CD36 from a contractioninducible intracellular storage compartment. Diabetes 52:1627-1634, 2003 F atty acid translocase (FAT)/CD36 is increasingly becoming recognized as a physiologically important long-chain fatty acid (FA) transport facilitator within the sarcolemma of muscle tissues (1-3). We have gathered convincing evidence that FAT/ CD36-mediated FA uptake is a rate-limiting step in FA use by heart and skeletal muscle (2). Moreover, FA uptake appears to be regulated by translocation of FAT/CD36 from intracellular, presumably endosomal, stores to the sarcolemma. Insulin and cellular contractions are two important physiological factors able to recruit FAT/CD36 to the sarcolemma (4 -7). Interestingly, the stimulation of FA uptake by contractions was additive to that of insulin, indicating that both factors operate through independent mechanisms. Furthermore, wortmannin completely blocked insulin-inducible FA uptake but had no effect on contraction-inducible FA uptake. Altogether, these findings indicate that insulin-inducible and contraction-inducible FAT/ CD36 pools are stored in two distinct intracellular sites (7). Strikingly, the effects of insulin and contractions on FA uptake by translocation of FAT/CD36 are remarkably similar to their effects on glucose uptake by translocation of the glucose transporter GLUT4 from insulin-inducible and contraction-inducible intracellular stores (7). Whereas the wortmannin sensitivity of insulin-inducible FA uptake indicates an involveme...

show abstract

“…Because of the tight coupling between FA oxidation and FA uptake, oligomycin would be expected to reduce FA uptake under these anaerobic conditions rather than to stimulate it. However, a recent study has demonstrated that the concentration of oligomycin required for 50% inhibition (IC 50 ) of the mitochondrial F 1 F 0 -ATPase is fivefold lower than its IC 50 for inhibition of electron flux through the respiratory chain [130]. This discrepancy opens a window of oligomycin concentrations at which the [74].…”

Section: Regulation By Contractionmentioning

confidence: 99%

Regulation of cardiac long-chain fatty acid and glucose uptake by translocation of substrate transporters

Luiken

Coort

Koonen

et al. 2004

Pflugers Arch - Eur J Physiol

152

103

View full text Add to dashboard Cite

Cardiac uptake of long-chain fatty acids (FA) is mediated predominantly by two membrane-associated proteins, the 43-kDa plasma membrane fatty acid-binding protein (FABPpm) and the 88-kDa fatty acid translocase/CD36 (FAT/CD36). While FABPpm is present constitutively in the sarcolemma, FAT/CD36 is recycled between an intracellular membrane compartment and the sarcolemma. Since the amount of sarcolemmal FAT/CD36 is a major determinant of cellular FA uptake, understanding of the regulation of its recycling is likely to provide new insights into altering substrate preference of the heart. FAT/CD36 recycling displays a remarkable similarity with that of the two glucose transporters (GLUT) in the heart, GLUT1 and GLUT4. Translocation of all three transporters is induced by insulin and by contraction, which stimuli activate distinct signalling cascades. The insulin pathway involves phosphatidylinositol-3 kinase (PI3K) whilst the contraction pathway is dependent on AMP-activated protein kinase (AMPK). For the identification of additional protein components involved in the regulation of FAT/CD36 recycling, valuable lessons can be learned from GLUT1 and GLUT4 recycling. Especially GLUT4 recycling is an intensively studied process in which a number of signalling proteins, both upstream and downstream from PI3 K and AMPK, have been identified, as well as proteins that are part of the translocation machinery involving Rab GTPases and soluble N-ethylmaleimide attachment protein receptors (SNAREs). Comparison of the magnitude of the effects of insulin and contraction on substrate uptake and on transporter appearance in the sarcolemma have revealed that FAT/CD36 recycling resembles GLUT1 recycling more closely than that of GLUT4. This pinpoints the recycling compartment and excludes a pre-endosomal storage compartment as the intracellular storage site for FAT/CD36. Further research will probably establish whether FAT/CD36 translocation is (partly) coupled to that of one or both GLUTs or, alternatively, whether it is a distinct process that also can be induced independently of GLUT1 or GLUT4 movement. In the latter case, a unique set of proteins would be dedicated to FAT/CD36 recycling, which would then provide an attractive target for manipulating cardiac substrate preference.

show abstract

Reversible ischemic inhibition of F1F0-ATPase in rat and human myocardium

Cited by 39 publications

References 33 publications

Valsartan improves mitochondrial function in hearts submitted to acute ischemia

Valsartan improves mitochondrial function in hearts submitted to acute ischemia

Contraction-Induced Fatty Acid Translocase/CD36 Translocation in Rat Cardiac Myocytes Is Mediated Through AMP-Activated Protein Kinase Signaling

Regulation of cardiac long-chain fatty acid and glucose uptake by translocation of substrate transporters

Contact Info

Product

Resources

About