Novel perspective: exercise training stimulus triggers the expression of the oncoprotein human double minute-2 in human skeletal muscle

Autor: Olivier Birot, Fares Gouzi, Dara Slopack, Julian Aiken, Tara L. Haas, Maurice Hayot, Thomas Gustafsson, Jacques Mercier, Emilie Roudier
Přispěvatelé: Angiogenesis Research Group [Toronto, Canada] (Faculty of Health), York University [Toronto], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Department of Laboratory Medicine [Stockholm, Sweden] (Section of Clinical Physiology), Karolinska Institutet [Stockholm], This study was supported by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada to O. B., funding from the Faculty of Health at York University to O. B., the France-Canada Research Fund 2011 to J. M. and O. B., and joint grants from the CHRU Montpellier, patients associations and APARD. F. G. was supported by a CIFRE grant from the Fontalvie Corporation and the French Ministère délégué à la recherche et aux nouvelles technologies., Gouzi, Fares, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2013
Předmět:
medicine.medical_specialty
Physiology
Angiogenesis
[SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
PECAM-1
FOXO1
law.invention
03 medical and health sciences
0302 clinical medicine
Mdm2
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
law
Physiology (medical)
Internal medicine
medicine
[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
Platelet
Transcription factor
ComputingMilieux_MISCELLANEOUS
Original Research
030304 developmental biology
0303 health sciences
biology
business.industry
Skeletal muscle
[SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Endothelial stem cell
Endocrinology
medicine.anatomical_structure
FoxO1
030220 oncology & carcinogenesis
Immunology
biology.protein
Suppressor
business
Zdroj: Physiological Reports
Physiological Reports, Wiley, 2013, 1 (2), pp.e00028. ⟨10.1002/phy2.28⟩
Physiological Reports, 2013, 1 (2), pp.e00028. ⟨10.1002/phy2.28⟩
ISSN: 2051-817X
Popis: High expression levels of human double minute-2 (Hdm2) are often associated with increased risk of cancer. Hdm2 is well established as an oncoprotein exerting various tumorigenic effects. Conversely, the physiological functions of Hdm2 in nontumor cells and healthy tissues remain largely unknown. We previously demonstrated that exercise training stimulates expression of murine double minute-2 (Mdm2), the murine analog of Hdm2, in rodent skeletal muscle and Mdm2 was required for exercise-induced muscle angiogenesis. Here we showed that exercise training stimulated the expression of Hdm2 protein in human skeletal muscle from +38% to +81%. This robust physiological response was observed in 60-70% of the subjects tested, in both young and senior populations. Similarly, exercise training stimulated the expression of platelet endothelial cell adhesion molecule-1, an indicator of the level of muscle capillarization. Interestingly, a concomitant decrease in the tumor suppressor forkhead box O-1 (FoxO1) transcription factor levels did not occur with training although Mdm2/Hdm2 is known to inhibit FoxO1 expression in diseased skeletal muscle. This could suggest that Hdm2 has different targets when stimulated in a physiological context and that exercise training could be considered therapeutically in the context of cancer in combination with anti-Hdm2 drug therapies in order to preserve Hdm2 physiological functions in healthy tissues.
Databáze: OpenAIRE
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