Contraction-induced fatty acid translocase/CD36 translocation in rat cardiac myocytes is mediated through AMP-activated protein kinase signaling.
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 contraction-inducible FAT/CD36 translocation. The cell-permeable adenosine analog 5-aminoimidazole-4-carboxamide-1-beta-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 contraction-inducible intracellular storage compartment.
Luiken
Joost J F P
JJ
Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands. j.luiken@fys.unimaas.nl
Coort
Susan L M
SL
Willems
Jodil
J
Coumans
Will A
WA
Bonen
Arend
A
van der Vusse
Ger J
GJ
Glatz
Jan F C
JF
D055372:AMP-Activated Protein Kinases; D000255:Adenosine Triphosphate / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D004558:Electric Stimulation; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism*; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D009840:Oligomycins / Q000494:pharmacology; D027361:Organic Anion Transporters / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D012265:Ribonucleotides / Q000494:pharmacology; D015398:Signal Transduction
D018955:CD36 Antigens; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008562:Membrane Glycoproteins; D009097:Multienzyme Complexes; D009840:Oligomycins; D027361:Organic Anion Transporters; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide