Vitamin B12, a chlorophyll-related analog to pheophytin a from marine brown algae, promotes neurite outgrowth and stimulates differentiation in PC12 cells

Abstract

We previously isolated an analog to chlorophyll-related compounds, pheophytin a, from the marine brown alga Sargassum fulvellum and demonstrated that it is a neurodifferentiation compound. In the current study, we investigated the effects of the pheophytin a analog vitamin B 12 on PC12 cell differentiation. In the presence of a low level of nerve growth factor (10 ng ml -1 ), vitamin B 12 demonstrated neurite outgrowthpromoting activity in PC12 cells. The effect was dose-dependent in the range of 6-100 lM. In the absence of nerve growth factor, vitamin B 12 did not promote differentiation. To investigate the mechanism for this effect, we conducted differentiation assays and western blot analysis with signal transduction inhibitors and found that vitamin B 12 did not promote PC12 cell differentiation in the presence of K252a or U0126 inhibitors. These results suggest that vitamin B 12 stimulates PC12 cell differentiation through enhancement of the mitogen-activated protein kinase signal transduction pathway, which is also induced by nerve growth factor. Thus, vitamin B 12 may be a good candidate for treatment of neurodegenerative diseases such as Alzheimer's disease.

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