Novel effect of vitamin K(1) (phylloquinone) and vitamin K(2) (menaquinone) on promoting nerve growth factor-mediated neurite outgrowth from PC12D cells.

The nerve growth factor (NGF)-potentiating effect of K vitamins on PC12D cells was investigated. Treatment of PC12D cells with vitamin K(1) or K(2) in the presence of NGF significantly enhanced the proportion of neurite-bearing cells and acetylcholinesterase activity compared with NGF treatment alone. The K vitamins-enhanced neurite outgrowth on PC12D cells was completely blocked by a protein kinase A (PKA) inhibitor or mitogen-activated protein kinase (MAPK) kinase inhibitor PD98059, whereas a protein kinase C inhibitor chelerythrine chloride did not significantly inhibit the enhancing effect of the K vitamins. These results suggest that the K vitamins enhance neurite outgrowth via the activation of PKA and MAPK-mediated signaling pathways in PC12D cells.