Reduction of calcium flux from the extracellular region and endoplasmic reticulum by amorphous nano-silica particles owing to carboxy group addition on their surface.

Several studies have reported that amorphous nano-silica particles (nano-SPs) modulate calcium flux, although the mechanism remains incompletely understood. We thus analyzed the relationship between calcium flux and particle surface properties and determined the calcium flux route. Treatment of Balb/c 3T3 fibroblasts with nano-SPs with a diameter of 70 nm (nSP70) increased cytosolic calcium concentration, but that with SPs with a diameter of 300 or 1000 nm did not. Surface modification of nSP70 with a carboxy group also did not modulate calcium flux. Pretreatment with a general calcium entry blocker almost completely suppressed calcium flux by nSP70. Preconditioning by emptying the endoplasmic reticulum (ER) calcium stores slightly suppressed calcium flux by nSP70. These results indicate that nSP70 mainly modulates calcium flux across plasma membrane calcium channels, with subsequent activation of the ER calcium pump, and that the potential of calcium flux by nano-SPs is determined by the particle surface charge.

Amorphous nanosilica particles evoke vascular relaxation through PI3K/Akt/eNOS signaling.

There have been several reported studies on the distribution and/or toxicity of nanosilica particles. However, the influence of these particles on blood vessels through which they are distributed is poorly understood. Hence, we investigated the effects of nano- and micromaterials on blood vessel shrinkage and relaxation. Nanosilica particles with diameters of 70 nm (nSP70) were used as the nanomaterial, and particles of 300 and 1000 nm (nSP300 and mSP1000, respectively) were used as micromaterials. A rat thoracic aorta was used as the test blood vessel. The nano- and micromaterials had no effect on vessel shrinkage. Of the nano- and micromaterials tested, only nSP70 strongly evoked vascular relaxation. Vascular relaxation evoked by nSP70 was almost completely inhibited by the phosphoinositide 3-kinase (PI3K) inhibitor wortmannin. In addition, the selective nitric oxide synthesis inhibitor NG-nitro-l-arginine methyl ester, which inhibits endothelial nitric oxide synthase (eNOS) downstream of PI3K signaling, inhibited vascular relaxation evoked by nSP70. In an analysis using bovine aortic endothelial cells (bAECs), nSP70 phosphorylated protein kinase B (AKT) and eNOS acted downstream of PI3K signaling. PI3K inhibition by wortmannin reduced AKT and eNOS phosphorylation. These results demonstrated that 70-nm amorphous nanosilica particles evoked vascular relaxation through PI3K/Akt/eNOS signaling. Moreover, it was suggested that nanomaterials, in general, control or disrupt vascular function by activating a known signal cascade.