AlphaB-crystallin is involved in oxidative stress protection determined by VEGF in skeletal myoblasts.
Recent studies suggest that the effects of VEGF-A, the prototype VEGF ligand, may extend to a variety of cell types other than endothelial cells. The expression of VEGF-A and its main receptors, Flt-1/VEGFR-1 and KDR/Flk-1/VEGFR-2, was indeed detected in several cell types, including cardiac myocytes and regenerating myotubes. In addition to its proangiogenic activity, evidence indicates that VEGF-A can sustain skeletal muscle regeneration by enhancing the survival and migration of myogenic cells and by promoting the growth of myogenic fibers. In this study, our aim was to investigate whether VEGF could protect skeletal muscle satellite cells from apoptotic cell death triggered by reactive oxygen species and to identify the main molecular mechanisms. C2C12 mouse myoblasts, cultured in vitro in the presence of exogenous VEGF or stably transfected with a plasmid vector expressing VEGF-A, were subjected to oxidative stress and analyzed for cell growth and survival, induction of apoptosis, and molecular signaling. The results of our study demonstrated that VEGF protects C2C12 myoblasts from apoptosis induced by oxidative or hypoxic-like stress. This protection did not correlate with the modulation of the expression of VEGF receptors, but is clearly linked to the phosphorylation of the KDR/Flk-1 receptor, the activation of NF-kappaB, and/or the overexpression of the antiapoptotic protein alphaB-crystallin.
Mercatelli
Neri
N
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, 00133 Rome, Italy.
Dimauro
Ivan
I
Ciafré
Silvia Anna
SA
Farace
Maria Giulia
MG
Caporossi
Daniela
D
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D032448:Myoblasts, Skeletal / Q000187:drug effects / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D034622:RNA Interference; D012038:Regeneration; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D038203:alpha-Crystallin B Chain / Q000096:biosynthesis / Q000502:physiology*; D051020:bcl-X Protein / Q000502:physiology
C494812:Bcl2l1 protein, mouse; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; D038203:alpha-Crystallin B Chain; D051020:bcl-X Protein; D006861:Hydrogen Peroxide; D040301:Vascular Endothelial Growth Factor Receptor-2