Phosphorus nuclear magnetic resonance spectroscopy of cardiac and skeletal muscles

Ingwall, J. S.

doi:10.1152/ajpheart.1982.242.5.h729

Cited by 108 publications

(74 citation statements)

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“…AICAR has been frequently used to activate AMP kinase (11)(12)(13). Its phosphorylated product has been observed to gradually accumulate in hepatocyte incubations up to 60 min.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, we have established that cAMP-dependent protein kinase A is not involved in regulation of FA uptake (8). Another likely candidate-signaling enzyme could be AMPactivated protein kinase, which has been firmly established to be involved in translocation of GLUT4 during an increase in contractile activity (9,10).During such an increase in mechanical performance, the high constitutive activity of adenylate kinase in the heart prevents a drastic fall in ATP via the conversion of two molecules of ADP into ATP and AMP (11,12). This process also renders the intracellular concentration of AMP a sensitive indicator of the metabolic state of the cell.…”

mentioning

confidence: 99%

“…During such an increase in mechanical performance, the high constitutive activity of adenylate kinase in the heart prevents a drastic fall in ATP via the conversion of two molecules of ADP into ATP and AMP (11,12). This process also renders the intracellular concentration of AMP a sensitive indicator of the metabolic state of the cell.…”

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confidence: 99%

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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

264

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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...

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“…AICAR has been frequently used to activate AMP kinase (11)(12)(13). Its phosphorylated product has been observed to gradually accumulate in hepatocyte incubations up to 60 min.…”

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

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

264

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“…In normal skeletal muscle, PCr acts as a rapid, transient source to replenish ATP by the CK reaction after each contraction, with changes in PCr observed on a millisecond time scale (6). Cyclic changes in PCr during the cardiac-contraction cycle have also been described in some (49)(50)(51)(52), but not all (53)(54)(55) reports. To the extent that cardiac muscle shares some properties with skeletal muscle (6), rapid provision of ATP by CK with contraction would represent a potentially important mechanism by which a significant reduction in CK flux in heart failure could limit temporal buffering and, thereby, limit contractile ATP supply and function.…”

Section: Fig 2 the Forward Cardiac Ck Flux Is Reduced In Chronic Hementioning

confidence: 99%

ATP flux through creatine kinase in the normal, stressed, and failing human heart

Weiss

Gerstenblith

Bottomley

2005

Proc. Natl. Acad. Sci. U.S.A.

294

348

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The heart consumes more energy per gram than any other organ, and the creatine kinase (CK) reaction serves as its prime energy reserve. Because chemical energy is required to fuel systolic and diastolic function, the question of whether the failing heart is ''energy starved'' has been debated for decades. Despite the central role of the CK reaction in cardiac energy metabolism, direct measures of CK flux in the beating human heart were not previously possible. Using an image-guided molecular assessment of endogenous ATP turnover, we directly measured ATP flux through CK in normal, stressed, and failing human hearts. We show that cardiac CK flux in healthy humans is faster than that estimated through oxidative phosphorylation and that CK flux does not increase during a doubling of the heart rate-blood pressure product by dobutamine. Furthermore, cardiac ATP flux through CK is reduced by 50% in mild-to-moderate human heart failure (1.6 ؎ 0.6 vs. 3.2 ؎ 0.9 mol͞g of wet weight per sec, P < 0.0005). We conclude that magnetic resonance strategies can now directly assess human myocardial CK energy flux. The deficit in ATP supplied by CK in the failing heart is cardiac-specific and potentially of sufficient magnitude, even in the absence of a significant reduction in ATP stores, to contribute to the pathophysiology of human heart failure. These findings support the pursuit of new therapies that reduce energy demand and͞or augment energy transfer in heart failure and indicate that cardiac magnetic resonance can be used to assess their effectiveness.heart failure ͉ magnetic resonance spectroscopy ͉ metabolism A TP provides the chemical energy that fuels myocardial contractile function. Relatively large rates of ATP synthesis are required to sustain normal systolic and diastolic function. The ''energy starvation'' hypothesis of heart failure suggests that inadequate ATP supply underlies the contractile dysfunction present in heart failure (1, 2). Large-scale clinical trials demonstrating that pharmacologic agents such as beta-blockers and angiotensin-converting enzyme inhibitors that reduce metabolic demand improve outcomes in heart failure, whereas those such as positive inotropic agents that increase energetic demand worsen outcomes (3) are consistent with the energy-starvation hypothesis. However, the ability to test the energy-starvation hypothesis has been limited, in part, by an inability to directly measure ATP synthesis in the human heart.Creatine kinase (CK) is central to mammalian energy metabolism and serves as the prime energy reserve of the heart. CK reversibly converts ADP and creatine phosphate (PCr) to ATP and creatine (Cr). This reaction allows tight control of ADP and ATP concentrations in cardiac and skeletal muscle as well as in brain, providing a rapid source of ATP during ischemia and burst activity in skeletal muscle (4-6). It is also hypothesized that the CK reaction serves as an intracellular spatial energy shuttle, facilitating the transfer of high-energy phosphates from the mitochondria (where AT...

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“…Shimming appeared to be most reproducible and optimal when the thorax was filled with 2 ml 0.9% NaC1 (at 37 o C) fully immersing the heart. This phenomenon of magnetic susceptibility matching [17] has also been reported to improve the resolution in 31p-NMR spectra of isolated, prefused hearts [18]. The line width of the H20 signal was generally in the range of 40-60 Hz.…”

Section: Methodsmentioning

confidence: 83%

Effects of the anti-cancer drug adriamycin on the energy metabolism of rat heart as measured by in vivo 31P-NMR and implications for adriamycin-induced cardiotoxicity

Nicolay¹,

Aue

Seelig

et al. 1987

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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In vivo 31p-NMR was used to measure the effects of the anti-tumor drug adriamycin on the energy metabolism of rat heart. The exclusive acquisition of NMR signal from cardiac muscle was assured by positioning a solenoidal radio-frequency NMR coil around the heart. Appropriate control experiments verified that 31p-NMR spectra solely originated from this organ. Acute effects occurring shortly after adriamycin administration are expressed in 31p spectra as a dose-dependent decline in the cardiac levels of phosphocreatine, after which stabilization at a new steady-state level occurs. These acute effects of a single dose are complete in 30-60 min and no significant further changes take place within 150 min after drug introduction. Longer-term effects of single high doses and of multiple lower doses were measured up to a week after the initiation of treatment. It seemed that at a total dose of 20 mg/kg, drug-induced interference with cardiac energy metabolism was more pronounced than at the same dose in the acute phase. These 31p-NMR data demonstrate that adriamycin treatment is accompanied by a decrease of the cardiac phosphocreatine/ATP ratio which might be an expression of the well-established cardiotoxicity of the drug.

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Phosphorus nuclear magnetic resonance spectroscopy of cardiac and skeletal muscles

Cited by 108 publications

References 0 publications

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

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

ATP flux through creatine kinase in the normal, stressed, and failing human heart

Effects of the anti-cancer drug adriamycin on the energy metabolism of rat heart as measured by in vivo 31P-NMR and implications for adriamycin-induced cardiotoxicity

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