Premium
Exercise‐induced angiogenesis: When Murine Double Minute‐2 and Vascular Endothelial Growth factor run together for more capillaries
Author(s) -
ROUDIER Emilie,
BIROT Olivier
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.625.1
Subject(s) - angiogenesis , ex vivo , vascular endothelial growth factor , skeletal muscle , mdm2 , in vivo , regulator , medicine , chemistry , endocrinology , microbiology and biotechnology , biology , cancer research , vegf receptors , biochemistry , apoptosis , gene
Running exercise has been described as a physiological stimulus for skeletal muscle angiogenesis. Recent data, mostly from tumor cells studies, have evidenced that the Murine Double Minute‐2 (Mdm2) oncoprotein, the main negative regulator of p53, exerts itself some angiogenic effects, mainly by stimulating endothelial cells migration. Objectives We investigated whether exercise regulated Mdm2 and whether Mdm2 could thus represent a new actor of exercise‐induced muscle angiogenesis. Methods We developed an innovative model of ex vivo muscle explant culture allowing the time‐course study of muscle angiogenesis. Plantaris muscles from sedentary or active (70‐90 min exercise on a running treadmill, 12% slope, 25 m/min) Sprague‐Dawley rats were used for protein measurements and our ex vivo angiogenesis assay. Results We showed that 1) Mdm2 protein was strongly activated by phosphorylation on Ser166 in response to exercise, 2) exercise stimulated endothelial cells migration in our ex vivo muscle explant model, 3) such exercise‐induced angiogenic effect is dependant on Mdm2 activation, 4) Mdm2 activation is mediated by the Vascular Endothelial Growth Factor (VEGF) ‐ Extracellular signal‐regulated kinase 1/2 (ERK1/2) pathway. Conclusion Mdm2 is a new key actor of exercise‐induced angiogenesis in rat skeletal muscle. This work was supported by the Natural Sciences and Engineering Research Council of Canada.