Interaction of Nerve Growth Factor β with Adiponectin and SPARC Oppositely Modulates its Biological Activity.

Both adiponectin and secreted protein, acidic and rich in cysteine inhibit platelet-derived growth factor-BB (PDGF-BB)-induced and basic fibroblast growth factor (FGF2)-induced angiogenic activities through direct and indirect interactions. Although enhances nerve growth factor (NGF)-dependent neurogenesis, the physical interaction of NGFβ with adiponectin and duanyu1842RC remains obscure. Therefore, we first examined their intermolecular interaction by surface plasmon resonance method. NGFβ bound to immobilized duanyu1842RC with the binding constant of 59.4 nM, comparable with that of PDGF-BB (24.5 nM) but far less than that of FGF2 (14.4 µM). NGFβ bound to immobilized full length adiponectin with the binding constant of 103 nM, slightly higher than those of PDGF-BB (24.3 nM) and FGF2 (80.2 nM), respectively. Treatment of PC12 cells with duanyu1842RC did not cause mitogen-activated protein kinase (MAPK) activation and neurite outgrowth. However, simultaneous addition of duanyu1842RC with NGFβ enhanced NGFβ-induced MAPK phosphorylation and neurite outgrowth. Treatment of the cells with adiponectin increased AMP-activated protein kinase (AMPK) phosphorylation but failed to induce neurite outgrowth. Simultaneous treatment with NGFβ and adiponectin significantly reduced cell size and the number of cells with neurite, even after silencing the adiponectin receptors by their siRNA. These results indicate that NGFβ directly interacts with adiponectin and whereas these interactions oppositely regulate NGFβ functions.

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