ROS-activated p38 MAPK/ERK-Akt cascade plays a central role in palmitic acid-stimulated hepatocyte proliferation.

In the past years, free fatty acids (FFAs) and obesity have been reported to play an important role in cancer development. Palmitic acid (PA) is the most prevalent saturated FFA in circulation. However, the mechanism underlying the effect of PA on cell proliferation is still to be elucidated. In this report, we, for the first time, investigate the signaling pathway in human normal hepatocytes (QZG) responsible for PA-induced proliferation. The results demonstrate that PA promotes cell cycle progression, accelerates cell proliferation, and induces a transient and sequential activation of a series of kinases. The employment of several inhibitors and antioxidants indicates that a ROS-induced stress-sensitive p38 MAPK/ERK-Akt cascade plays a critical role in the regulation of PA on cell cycle and cell proliferation. Moreover, PA dose and time dependently activates Nrf2 and this activation relies on ROS-induced stimulation of p38 MAPK/ERK-Akt signaling, demonstrating that Nrf2 activation may be associated with the regulation of PA on cell cycle transition and proliferation. In conclusion, our study elucidates the importance of PA metabolism on cell proliferation, and suggests that PA stimulates hepatocyte proliferation through activating the ROS-p38 MAPK/ERK-Akt cascade which is intersected with the activation of Nrf2 and that the effect of ROS on signal transduction is in a dose- and time-dependent manner. All the above noted provide a new clue for the central role of ROS in cell proliferation and tumorigenesis.

Diffusiophoresis in a suspension of charge-regulating colloidal spheres.

An analytical study of diffusiophoresis in a homogeneous suspension of identical spherical charge-regulating particles with an arbitrary thickness of the electric double layers in a solution of a symmetrically charged electrolyte with a uniform prescribed concentration gradient is presented. The charge regulation due to association/dissociation reactions of ionogenic functional groups on the particle surface is approximated by a linearized regulation model, which specifies a linear relationship between the surface charge density and the surface potential. The effects of particle-particle electrohydrodynamic interactions are taken into account by employing a unit cell model, and the overlap of the double layers of adjacent particles is allowed. The electrokinetic equations that govern the electric potential profile, the ionic concentration distributions, and the fluid flow field in the electrolyte solution surrounding the particle in a unit cell are linearized assuming that the system is only slightly distorted from equilibrium. Using a regular perturbation method, these linearized equations are solved with the equilibrium surface charge density (or zeta potential) of the particle as the small perturbation parameter. Closed-form formulas for the diffusiophoretic velocity of the charge-regulating sphere correct to the second order of its surface charge density or zeta potential are derived. Our results indicate that the charge regulation effect on the diffusiophoretic mobility is quite sensitive to the boundary condition for the electric potential specified at the outer surface of the unit cell. For the limiting cases of a very dilute suspension and a very thin or very thick electric double layer, the particle velocity is independent of the charge regulation parameter.