title: Leukemia inhibitory factor reduces contractile function and induces alterations in energy metabolism in isolated cardiomyocytes.
abstract: 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.
authors.affiliation: Institute for Experimental Medical Research, Ullevaal University Hospital, University of Oslo, 0407 Oslo, Norway. geir.florholmen@medisin.uio.no
authors.forename: Geir
authors.initials: G
authors.lastname: Florholmen
authors.forename: Vigdis
authors.initials: V
authors.lastname: Aas
authors.forename: Arild Christian
authors.initials: AC
authors.lastname: Rustan
authors.forename: Per Kristian
authors.initials: PK
authors.lastname: Lunde
authors.forename: Nadine
authors.initials: N
authors.lastname: Straumann
authors.forename: Hilde
authors.initials: H
authors.lastname: Eid
authors.forename: Annlaug
authors.initials: A
authors.lastname: Odegaard
authors.forename: Hilde
authors.initials: H
authors.lastname: Dishington
authors.forename: Kristin Brevik
authors.initials: KB
authors.lastname: Andersson
authors.forename: Geir
authors.initials: G
authors.lastname: Christensen
mesh_terms: 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
chemical_list: D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D009243:NAD; D019301:Oleic Acid; D000255:Adenosine Triphosphate; D025261:Mitochondrial Proton-Translocating ATPases; D005947:Glucose