Leukemia inhibitory factor reduces contractile function and induces alterations in energy metabolism in isolated cardiomyocytes.
Interleukin (IL)-6 related cytokines may be involved in the pathophysiology of heart failure. Leukemia inhibitory factor (LIF) is an IL-6 related cytokine, and elevated levels of LIF have been found in failing hearts. The aim of our study was to investigate how LIF may influence isolated cardiomyocytes. Adult cardiomyocytes were isolated from male Wistar rat hearts and treated with 1 nM LIF for 48 h. Contractile function was measured using a video-edge detection system. Fractional shortening was reduced at 0.25 Hz in LIF treated cells (7.4% +/- 0.5%) compared to control cells (9.0% +/- 0.7%). Gene expression analysis showed that expression of the mitochondrial ATP-synthase F(1) alpha subunit was reduced in cells exposed to LIF. The activity of the enzyme was also reduced in these cells (0.10 +/- 0.05 mumol/min per mg protein) compared to controls (1.23 +/- 0.40 mumol/min per mg protein). The levels of ATP and creatine phosphate were reduced by 15.0% +/- 3.0% and 11.2% +/- 2.7% in LIF treated cells. LIF increased both (3)H-deoxyglucose uptake and lactate levels, suggesting an increase in anaerobic energy metabolism. Beta-oxidation of (14)C-oleic acid was increased by 51.2% +/- 14.1% following LIF treatment, but no changes were found in cellular uptake or oxidation of (14)C-oleic acid to CO(2). In conclusion, LIF induces contractile dysfunction and changes in energy metabolism in isolated cardiomyocytes.
Florholmen
Geir
G
Institute for Experimental Medical Research, Ullevaal University Hospital, University of Oslo, 0407 Oslo, Norway. geir.florholmen@medisin.uio.no
Aas
Vigdis
V
Rustan
Arild Christian
AC
Lunde
Per Kristian
PK
Straumann
Nadine
N
Eid
Hilde
H
Odegaard
Annlaug
A
Dishington
Hilde
H
Andersson
Kristin Brevik
KB
Christensen
Geir
G
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D015850:Interleukin-6 / Q000494:pharmacology*; D053605:Leukemia Inhibitory Factor; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D025261:Mitochondrial Proton-Translocating ATPases / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D009243:NAD / Q000378:metabolism; D019301:Oleic Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D009243:NAD; D019301:Oleic Acid; D000255:Adenosine Triphosphate; D025261:Mitochondrial Proton-Translocating ATPases; D005947:Glucose