Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9426719 | Neuroscience | 2005 | 11 Pages |
Abstract
We previously found that the methanol extract of a marine brown alga, Sargassum macrocarpum showed marked nerve growth factor (NGF)-dependent neurite outgrowth promoting activity to PC12D cells. The active substance purified was elucidated to be sargachromenol. The median effective dose (ED50) was 9 μM against PC12D cells in the presence of 10 ng/ml NGF, although it showed no neurotrophic effect on its own. Pretreatment of cells with protein kinase A (PKA) inhibitor or U0126 substantially suppressed the sargachromenol-enhanced neurite outgrowth from PC12D cells, suggesting that the activation of cyclic AMP-mediated protein kinase and mitogen-activated protein (MAP) kinase 1/2 was apparently required for the action of sargachromenol. On the other hand, sargachromenol significantly promoted the survival of neuronal PC12D cells at 0-50 ng/ml NGF in serum-free medium. Neither PKA inhibitor nor U0126 could inhibit the survival supporting effect of sargachromenol, whereas wortmannin significantly blocked the sargachromenol-induced survival supporting effect on neuronal PC12D cells, suggesting that sargachromenol rescued neuronal PC12D cells by activating phosphatidylinositol-3 kinase. These results demonstrate that sargachromenol promotes neuronal differentiation of PC12D cells and supports the survival of neuronal PC12D cells via two distinct signaling pathways.
Keywords
PBSED50NGFpKaERKHEPESFBSJnkPI3KSDSDMEMc-Jun N-terminal protein kinaseN-[2-hydroxyethyl]piperazine-N′-[2-ethanesulfonic acid]EDTAEthylenediaminetetraacetic acidsodium dodecyl sulfatehorse serumfetal bovine serumnerve growth factorphosphatidylinositol-3 kinaseMethanolmedian effective dosePhosphate-buffered salineDulbecco’s modified eagle’s mediumMeOHmapmitogen-activated proteinprotein kinase Amitogen-activated protein kinaseextracellular signal-regulated kinase
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Authors
C.K. Tsang, A. Ina, T. Goto, Y. Kamei,