MS-430, a synthetic pyrimidine derivative, influences the intracellular signal transduction pathway leading to neuronal differentiation of PC12h cells

Journal of Biochemistry
T IkeuchiH Hatanaka

Abstract

Although NGF (nerve growth factor) induces neuronal differentiation of PC12 cells, EGF (epidermal growth factor) acts as a mitogen for these cells. We have studied the effects of a synthetic pyrimidine derivative, MS-430, on the NGF and EGF actions on PC12h cells. We found that MS-430 accelerated NGF-induced neurite extension of PC12h cells and that, in the presence of MS-430, PC12h cells extended neurites in response to EGF. Next, we investigated the tyrosine phosphorylation of NGF receptor TrkA and the EGF receptor (EGFR) as well as mitogen-activated protein kinase (MAPK), which is a key protein in the intracellular signal transduction pathway. It was found that MS-430 prolonged the EGF-induced phosphorylation of EGFR and MAPK compared to that without MS-430. MS-430 also prolonged the NGF-induced phosphorylation of MAPK, but the phosphorylation of TrkA induced by NGF was not affected by MS-430. These results suggest that MS-430 influences the intracellular signal transduction pathway which causes the neuronal differentiation of PC12h cells.

Citations

Apr 25, 2000·Biulleten' eksperimental'noĭ biologii i meditsiny·I S RaginovR Kh Khafiz'ianova
Jan 5, 2011·Journal of Neuroinflammation·Chinnasamy Elango, Sivasithambaram Niranjali Devaraj

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