Role of ERK1/2 activation in microtubule stabilization and glucose transport in cardiomyocytes
| Autor: | René Lerch, Mohamed Asrih, Corinne Pellieux, Irène Papageorgiou, Christophe Albert Montessuit |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Physiology Endocrinology Diabetes and Metabolism Glucose uptake Microtubules Rats Sprague-Dawley 0302 clinical medicine Stress Physiological/physiology Insulin Glucose/metabolism Myocytes Cardiac Enzyme Activation/drug effects/physiology Alitretinoin Cells Cultured ddc:616 0303 health sciences Mitogen-Activated Protein Kinase 3 Protein Stability Kinase Mitogen-Activated Protein Kinase 3/metabolism Myocytes Cardiac/drug effects/metabolism/physiology Biological Transport/drug effects/physiology 030220 oncology & carcinogenesis Mitogen-activated protein kinase medicine.medical_specialty Insulin/pharmacology MAP Kinase Signaling System Phosphatase Primary Cell Culture Tretinoin Biology 03 medical and health sciences Stress Physiological Microtubule Physiology (medical) Internal medicine medicine Protein Stability/drug effects Animals Protein kinase A 030304 developmental biology Tretinoin/pharmacology Microtubules/drug effects/metabolism Glucose transporter Biological Transport Microtubule organizing center Protein Multimerization/drug effects Rats Enzyme Activation Glucose Endocrinology biology.protein MAP Kinase Signaling System/drug effects/physiology Protein Multimerization |
| Zdroj: | American Journal of Physiology. Endocrinology and Metabolism, Vol. 301, No 5 (2011) pp. E836-43 American journal of physiology. Endocrinology and metabolism |
| ISSN: | 0193-1849 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|