Proteomic profiles of cultured cells stimulated with VEGFs dimers and search for natural compounds angiogenesis inhibitors

2010 - 2011Some members of the vascular endothelial growth factor (VEGF) family, such as VEGF and PlGF, and related receptors (KDR and Flt-1) play a key role in the modulation of angiogenesis, both physiological and pathological. For this reason they are considered valid therapeutic targets. Anti-angiogenesis therapy, despite the scientific efforts and promising results, is still suffering of some limitations. In the attempt to produce a research that can facilitate the future development of new antiangiogenic therapy strategies, we realized these goals: 1) carry out an expression proteomic study of cell coltures, after their treatment with some dimers of VEGF family; 2) identify new natural compounds able to inhibit the axis of interaction VEGF/Flt-1 and PlGF/Flt-1. We used gel-based proteomics to detect the differentially expressed proteins by VEGF, PlGF and VEGF/PlGF, in HUVECs and HEK-293-hFlt-1. Gels variability was also determined by principal component analysis (PCA)... [edited by Author]X n.s

Increased expression of Myosin binding protein H in the skeletal muscle of amyotrophic lateral sclerosis patients

AbstractAmyotrophic lateral sclerosis (ALS) is a severe and fatal neurodegenerative disease of still unknown pathogenesis. Recent findings suggest that the skeletal muscle may play an active pathogenetic role. To investigate ALS's pathogenesis and to seek diagnostic markers, we analyzed skeletal muscle biopsies with the differential expression proteomic approach. We studied skeletal muscle biopsies from healthy controls (CN), sporadic ALS (sALS), motor neuropathies (MN) and myopathies (M). Pre-eminently among several differentially expressed proteins, Myosin binding protein H (MyBP-H) expression in ALS samples was anomalously high. MyBP-H is a component of the thick filaments of the skeletal muscle and has strong affinity for myosin, but its function is still unclear. High MyBP-H expression level was associated with abnormal expression of Rho kinase 2 (ROCK2), LIM domain kinase 1 (LIMK1) and cofilin2, that might affect the actin–myosin interaction. We propose that MyBP-H expression level serves, as a putative biomarker in the skeletal muscle, to discriminate ALS from motor neuropathies, and that it signals the onset of dysregulation in actin–myosin interaction; this in turn might contribute to the pathogenesis of ALS