Leukemia inhibitory factor reduces contractile function and induces alterations in energy metabolism in isolated cardiomyocytes

Florholmen, Geir; Aas, Vigdis; Rustan, Arild C.; Lunde, Per; Straumann, Nadine; Eid, H.M.A.; Ødegaard, Annlaug; Dishington, Hilde; Andersson, Kristin B.; Christensen, Geir

doi:10.1016/j.yjmcc.2004.09.008

Cited by 22 publications

(14 citation statements)

References 33 publications

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“…Isolated cells were maintained in Medium 199 (Sigma, St. Louis, MO, USA) with 2 mg/ml BSA, 2 mmol/l DL-carnitine, 5 mmol/l creatine, 5 mmol/l taurine, 0.1 μmol/l insulin, 0.1 nmol/l triiodothyronine (all from Sigma), 100 U/ml penicillin (Invitrogen, Paisley, UK) and 100 μg/ml streptomycin (Invitrogen) with or without 1 nmol/l LIF (Chemicon, Temecula, CA, USA). This procedure yields approximately 75% rod-shaped cardiomyocytes after 48 h in culture as previously reported [5]. It has previously been shown that adult cardiomyocytes maintained in culture in a serum-free medium remain insulin responsive [16].…”

Section: Cardiomyocyte Culturessupporting

confidence: 63%

Section: Introductionmentioning

confidence: 86%

“…We recently showed that chronic LIF treatment reduced the ability to produce ATP and reduced cellular content of ATP in isolated cardiomyocytes [5]. We [5] and others [6] have found increased glucose uptake following LIF treatment for 48 h. It is not known whether acute LIF treatment has similar effects on the uptake of glucose. Insulin increases glucose uptake in cardiomyocytes by translocating the solute carrier family 2, member 4 (SLC2A4, previously known as glucose transporter 4 [GLUT4]) to the plasma membrane by activation of the phosphatidylinositol (PI) 3-kinase and Akt/protein kinase B (PKB) signalling pathway [7].…”

Section: Introductionmentioning

confidence: 86%

“…Isolated cardiomyocytes were plated on six-well culture dishes (Corning Int., Corning, NY, USA), and measurements of [ 3 H]deoxyglucose uptake were performed as described elsewhere [5]. In brief, the cells were maintained in culture for 48 h with or without 1 nmol/l LIF, washed twice with uptake buffer (in mmol/l) (140 NaCl, 20 HEPES, 5 KCl, 2.5 MgSO 4 , and 1 CaCl 2 ) and then incubated with the same buffer supplemented with 2-[ 3 H(G)]deoxy-D-glucose (American Radiolabeled Chemicals (ARC), Inc., MO, USA) (37 kBq/ ml) for 15 min.…”

Section: Deoxyglucose Transportmentioning

confidence: 99%

“…C]glucose (ARC) (7.4 kBq/ml) and 20 mmol/l HEPES. Measurements of glucose oxidation followed procedures described elsewhere [5]. Flasks containing no cells were used to correct for non-specific CO 2 trapping.…”

Section: Deoxyglucose Transportmentioning

confidence: 99%

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Leukaemia inhibitory factor stimulates glucose transport in isolated cardiomyocytes and induces insulin resistance after chronic exposure

et al. 2006

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Aims/hypothesis: Hypertrophic and failing hearts have increased utilisation of glucose, but also develop insulin resistance and reduced ability to produce ATP. Increased levels of the IL-6-related cytokine leukaemia inhibitory factor (LIF) are found in failing hearts, and we have recently shown that LIF reduces ATP production in isolated cardiomyocytes. In the present study we investigated effects of LIF on glucose metabolism, and how LIF-treated cells respond to insulin stimulation. Methods: Cardiomyocytes were isolated from adult Wistar rats by collagen digestion, maintained in culture for 48 h, and then treated with 1 nmol/l LIF. Results: Acute LIF treatment increased deoxyglucose uptake compared with controls, but no additive effect was observed in cardiomyocytes treated with LIF and insulin. The phosphatidylinositol 3-kinase inhibitor wortmannin did not affect LIF-induced glucose uptake. LIF had no effect on AMP-activated protein kinase phosphorylation. Cardiomyocytes treated with LIF for 48 h did not respond to insulin by increasing deoxyglucose uptake and showed a reduced insulin-mediated uptake of oleic acid and formation of complex lipids compared with control cells. Chronic LIF treatment increased gene expression of the suppressor of cytokine signalling (Socs) 3 and reduced expression of solute carrier family 2, member 4 (Slc2a4, previously known as glucose transporter 4 [Glut4]). In line with these observations, chronic LIF treatment reduced insulin-mediated phosphorylation of both Akt/protein kinase B (PKB) and glycogen synthase kinase (GSK)-3. Conclusions/interpretation: Acute LIF treatment increased glucose uptake in isolated cardiomyocytes by a pathway different from that of insulin. Chronic LIF treatment induced insulin resistance, possibly mediated by altered expression of Socs3 and Slc2a4, and impaired insulin-mediated phosphorylation of GSK-3 and Akt/PKB.

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Section: Cardiomyocyte Culturessupporting

confidence: 63%

Section: Introductionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 86%

Section: Deoxyglucose Transportmentioning

confidence: 99%

Section: Deoxyglucose Transportmentioning

confidence: 99%

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Leukaemia inhibitory factor stimulates glucose transport in isolated cardiomyocytes and induces insulin resistance after chronic exposure

et al. 2006

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Identification of ataxia‐associated mtDNA mutations (m.4052T>C and m.9035T>C) and evaluation of their pathogenicity in transmitochondrial cybrids

et al. 2009

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The potential pathogenicity of two homoplasmic mtDNA point mutations, 9035T>C and 4452T>C, found in a family afflicted with maternally transmitted cognitive developmental delay, learning disability, and progressive ataxia was evaluated using transmitochondrial cybrids. We confirmed that the 4452T>C transition in tRNA(Met) represented a polymorphism; however, 9035T>C conversion in the ATP6 gene was responsible for a defective F(0)-ATPase. Accordingly, mutant cybrids had a reduced oligomycin-sensitive ATP hydrolyzing activity. They had less than half of the steady-state content of ATP and nearly an 8-fold higher basal level of reactive oxygen species (ROS). Mutant cybrids were unable to cope with additional insults, i.e., glucose deprivation or tertiary-butyl hydroperoxide, and they succumbed to either apoptotic or necrotic cell death. Both of these outcomes were prevented by the antioxidants CoQ(10) and vitamin E, suggesting that the abnormally high levels of ROS were the triggers of cell death. In conclusion, the principal metabolic defects, i.e., energy deficiency and ROS burden, resulted from the 9035T>C mutation and could be responsible for the development of clinical symptoms in this family. Furthermore, antioxidant therapy might prove helpful in the management of this disease.

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Myocyte Metabolic Imaging with Hyperpolarised MRI

Miller

2017

Protocols and Methodologies in Basic Science and Clinical Cardiac MRI

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Leukemia inhibitory factor reduces contractile function and induces alterations in energy metabolism in isolated cardiomyocytes

Cited by 22 publications

References 33 publications

Leukaemia inhibitory factor stimulates glucose transport in isolated cardiomyocytes and induces insulin resistance after chronic exposure

Leukaemia inhibitory factor stimulates glucose transport in isolated cardiomyocytes and induces insulin resistance after chronic exposure

Identification of ataxia‐associated mtDNA mutations (m.4052T>C and m.9035T>C) and evaluation of their pathogenicity in transmitochondrial cybrids

Myocyte Metabolic Imaging with Hyperpolarised MRI

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