title: Oxidative stress induces caveolin 1 degradation and impairs caveolae functions in skeletal muscle cells.
abstract: Increased level of oxidative stress, a major actor of cellular aging, impairs the regenerative capacity of skeletal muscle and leads to the reduction in the number and size of muscle fibers causing sarcopenia. Caveolin 1 is the major component of caveolae, small membrane invaginations involved in signaling and endocytic trafficking. Their role has recently expanded to mechanosensing and to the regulation of oxidative stress-induced pathways. Here, we increased the amount of reactive oxidative species in myoblasts by addition of hydrogen peroxide (H2O2) at non-toxic concentrations. The expression level of caveolin 1 was significantly decreased as early as 10 min after 500 μM H2O2 treatment. This reduction was not observed in the presence of a proteasome inhibitor, suggesting that caveolin 1 was rapidly degraded by the proteasome. In spite of caveolin 1 decrease, caveolae were still able to assemble at the plasma membrane. Their functions however were significantly perturbed by oxidative stress. Endocytosis of a ceramide analog monitored by flow cytometry was significantly diminished after H2O2 treatment, indicating that oxidative stress impaired its selective internalization via caveolae. The contribution of caveolae to the plasma membrane reservoir has been monitored after osmotic cell swelling. H2O2 treatment increased membrane fragility revealing that treated cells were more sensitive to an acute mechanical stress. Altogether, our results indicate that H2O2 decreased caveolin 1 expression and impaired caveolae functions. These data give new insights on age-related deficiencies in skeletal muscle.
authors: Univ Bordeaux, Chimie et Biologie des Membranes et Nanoobjets, UMR 5248, F-33600 Pessac, France; CNRS, Chimie et Biologie des Membranes et Nanoobjets, UMR 5248, F-33600 Pessac, France; Bordeaux INP, Chimie et Biologie des Membranes et Nanoobjets, UMR 5248, F-33600 Pessac, France.
authors: Alexis
authors: A
authors: Mougeolle
authors: Univ Bordeaux, Chimie et Biologie des Membranes et Nanoobjets, UMR 5248, F-33600 Pessac, France; CNRS, Chimie et Biologie des Membranes et Nanoobjets, UMR 5248, F-33600 Pessac, France; Bordeaux INP, Chimie et Biologie des Membranes et Nanoobjets, UMR 5248, F-33600 Pessac, France.
authors: Sylvie
authors: S
authors: Poussard
authors: Univ Bordeaux, Chimie et Biologie des Membranes et Nanoobjets, UMR 5248, F-33600 Pessac, France; CNRS, Chimie et Biologie des Membranes et Nanoobjets, UMR 5248, F-33600 Pessac, France; Bordeaux INP, Chimie et Biologie des Membranes et Nanoobjets, UMR 5248, F-33600 Pessac, France.
authors: Marion
authors: M
authors: Decossas
authors: Institut Curie-Centre de Recherche, Membrane Dynamics and Mechanics of Intracellular Signaling Team, INSERM U1143, CNRS UMR 3666, Paris, France.
authors: Christophe
authors: C
authors: Lamaze
authors: Univ Bordeaux, Chimie et Biologie des Membranes et Nanoobjets, UMR 5248, F-33600 Pessac, France; CNRS, Chimie et Biologie des Membranes et Nanoobjets, UMR 5248, F-33600 Pessac, France; Bordeaux INP, Chimie et Biologie des Membranes et Nanoobjets, UMR 5248, F-33600 Pessac, France.
authors: Olivier
authors: O
authors: Lambert
authors: Univ Bordeaux, Chimie et Biologie des Membranes et Nanoobjets, UMR 5248, F-33600 Pessac, France; CNRS, Chimie et Biologie des Membranes et Nanoobjets, UMR 5248, F-33600 Pessac, France; Bordeaux INP, Chimie et Biologie des Membranes et Nanoobjets, UMR 5248, F-33600 Pessac, France.
authors: Elise
authors: E
authors: Dargelos
mesh_terms: D000818:Animals; D021941:Caveolae / Q000378:metabolism*; D051242:Caveolin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D005434:Flow Cytometry; D006861:Hydrogen Peroxide / Q000633:toxicity*; D051379:Mice; D008854:Microscopy, Electron; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011480:Protease Inhibitors / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D011480:Protease Inhibitors; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D046988:Proteasome Endopeptidase Complex