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Role of ERK1/2 activation in microtubule stabilization and glucose transport in cardiomyocytes

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Published in American Journal of Physiology. Endocrinology and Metabolism. 2011, vol. 301, no. 5, p. E836-43
Abstract We previously demonstrated that microtubule disruption impairs stimulation of glucose uptake in cardiomyocytes and that 9-cis retinoic acid (9cRA) treatment preserved both microtubule integrity and stimulated glucose transport. Herein we investigated whether 1) activation of the extracellular signal-regulated kinases (ERK1/2) is responsible for microtubule destabilization and 2) ERK1/2 inactivation may explain the positive effects of 9cRA on glucose uptake and microtubule stabilization. Adult rat cardiomyocytes in primary culture showed increased basal ERK1/2 phosphorylation. Cardiomyocytes exposed to inhibitors of the ERK1/2 kinase mitogen/extracellular signal-regulated kinase (MEK) 1/2 had preserved microtubular scaffold, including microtubule-organizing centers (MTOC), together with increased insulin and metabolic stress-stimulated glucose transport as well as signaling, thus replicating the effects of 9cRA treatment. Although 9cRA treatment did not significantly reduce global ERK1/2 activation, it markedly reduced perinuclear-activated ERK1/2 at the location of MTOC. 9cRA also triggered relocation of the ERK1/2 phosphatase mitogen-activated protein kinase phosphatase-3 from the cytosol to the nucleus. These results indicate that, in cardiomyocytes, microtubule destabilization, leading to impaired stimulation of glucose transport, is mediated by ERK1/2 activation, impacting on the MTOC. 9cRA acid restores stimulated glucose transport indirectly through compartmentalized inactivation of ERK1/2.
Keywords AnimalsBiological Transport/drug effects/physiologyCells, CulturedEnzyme Activation/drug effects/physiologyGlucose/metabolismInsulin/pharmacologyMAP Kinase Signaling System/drug effects/physiologyMaleMicrotubules/drug effects/metabolismMitogen-Activated Protein Kinase 3/metabolismMyocytes, Cardiac/drug effects/metabolism/physiologyPrimary Cell CultureProtein Multimerization/drug effectsProtein Stability/drug effectsRatsRats, Sprague-DawleyStress, Physiological/physiologyTretinoin/pharmacology
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PMID: 21771966
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Article (Published version) (557 Kb) - document accessible for UNIGE members only Limited access to UNIGE
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Research group Ophtalmologie expérimentale (925)
Project FNS: 310000–122001
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ASRIH, Mohamed et al. Role of ERK1/2 activation in microtubule stabilization and glucose transport in cardiomyocytes. In: American Journal of Physiology. Endocrinology and Metabolism, 2011, vol. 301, n° 5, p. E836-43. https://archive-ouverte.unige.ch/unige:88465

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Deposited on : 2016-10-28

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