Binding of ATP to vascular endothelial growth factor isoform VEGF-A165 is essential for inducing proliferation of human umbilical vein endothelial cells

<p>Abstract</p> <p>Background</p> <p>ATP binding is essential for the bioactivity of several growth factors including nerve growth factor, fibroblast growth factor-2 and brain-derived neurotrophic factor. Vascular endothelial growth factor isoform 165 (VEGF-A₁₆₅) induces the proliferation of human umbilical vein endothelial cells, however a dependence on ATP-binding is currently unknown. The aim of the present study was to determine if ATP binding is essential for the bioactivity of VEGF-A₁₆₅.</p> <p>Results</p> <p>We found evidence that ATP binding toVEGF-A₁₆₅induced a conformational change in the secondary structure of the growth factor. This binding appears to be significant at the biological level, as we found evidence that nanomolar levels of ATP (4-8 nm) are required for the VEGF-A₁₆₅-induced proliferation of human umbilical vein endothelial cells. At these levels, purinergic signaling by ATP <it>via </it>P2 receptors can be excluded. Addition of alkaline phosphate to cell culture lowered the ATP concentration in the cell culture medium to 1.8 nM and inhibited cell proliferation.</p> <p>Conclusions</p> <p>We propose that proliferation of endothelial cells is induced by a VEGF-A₁₆₅-ATP complex, rather than VEGF-A₁₆₅alone.</p

Childhood emotional trauma and cyberbullying perpetration among emerging adults: a multiple mediation model of the role of problematic social media use and psychopathology

Research suggests that a small minority of social media users experience problems as a result of their online use. The purpose of the present study was to examine the association of cyberbullying perpetration and problematic social media use with childhood emotional trauma, Cluster B (narcissistic, histrionic, antisocial, and borderline) personality traits, dissociative experiences (DEs), depression, and self-esteem in a nonclinical undergraduate sample. A total of 344 university students volunteered to complete a questionnaire that included measures on the aforementioned dimensions. Thirty-eight percent of the participants had emotional neglect and 27% had emotional abuse, while 44% of them demonstrated at least one cyberbullying perpetration behavior. Results indicated that cyberbullying perpetrators had higher scores on problematic social media use, dissociative experiences, Cluster B traits, depression and childhood emotional trauma, and lower on self-esteem. Path analysis demonstrated that, while adjusting for gender and age, childhood emotional trauma was directly and indirectly associated with cyberbullying perpetration via Cluster B traits. Moreover, depression and dissociation were directly associated with problematic social media use. The findings of this study emphasize the important direct role of childhood emotional trauma and pathological personality traits on cyberbullying perpetration